Syria had been under Roman rule for seven centuries prior to the Arab Muslim conquest and had been invaded by the Sassanid Persians on a number of occasions during the 3rd, 6th and 7th centuries; it had also been subject to raids by the Sassanids' Arab allies, the Lakhmids.

During the Roman period, beginning after the fall of Jerusalem in the year 70, the entire region (Judea, Samaria, and the Galilee) was renamed Palaestina. During the last of the Roman-Persian Wars, beginning in 603, the Persians under Khosrau II had succeeded in occupying Syria, Palestine and Egypt for over a decade before being forced by the victories of Heraclius to conclude the peace of 628. Thus, on the eve of the Muslim conquests the Romans (or Byzantines as modern Western historians conventionally refer to Romans of this period) were still in the process of rebuilding their authority in these territories, which in some areas had been lost to them for almost twenty years.

The Byzantine (Roman) Emperor Heraclius, after re-capturing Syria from the Sassanians, set up new defense lines from Gaza to the south end of the Dead Sea. These lines were only designed to protect communications from bandits, and the bulk of the Byzantine defenses were concentrated in Northern Syria facing the traditional foes, the Sassanid Persians. The drawback of this defense line was that it enabled the Muslims, advancing from the desert in the south, to reach as far north as Gaza before meeting regular Byzantine troops.

After successful campaigns against the Sassanids and the ensuing conquest of Iraq, Khalid established his stronghold in Iraq. While engaged with Sassanid forces, he also confronted the Ghassanids, Arab clients of the Byzantines. Medina soon recruited tribal contingents from all over the Arabian peninsula. The tradition of raising armies from tribal contingents remained in use until 636, when Caliph Umar organised the army as a state department. Abu Bakr organised the army into four corps, each with its own commander and objective.

• Amr ibn al-A'as: Objective Palestine. Move on Elat route, then across Valley of Arabah.
• Yazid ibn Abu Sufyan: Objective Damascus. Move on Tabuk route.
• Shurahbil ibn Hasana: Objective Jordan. Move on Tabuk route after Yazid.
• Abu Ubaidah ibn al-Jarrah: Objective Emesa. Move on Tabuk route after Shurahbil.

Not knowing the precise position of the Byzantine army, Abu Bakr ordered that all corps should remain in touch with each other so that they could render assistance if the Byzantines were able to concentrate their army in any operational sector. In case the corps had to concentrate for one major battle, Abu Ubaidah was appointed Commander-in-Chief of the entire army.

The Emperor Heraclius, having received intelligence of the movements of the Muslim armies from his Arab clients, began to plan countermeasures. Upon Heraclius' orders, Byzantine forces from different garrisons in the north started moving to gather at Ayjnadyn.

Abu Ubaidah informed the Caliph about the preparations made by the Byzantines in the third week of May 634. Because Abu Ubaida didn't have experience as a commander of military forces in such major operations, especially against the powerful Roman Army, Abu Bakr decided to send Khalid ibn Walid to assume command.

Khalid immediately set out for Syria from Al-Hirah, in Iraq, in early June, taking with him half his army, about 8000 strong. Khalid selected a shorter route to Syria, an unconventional route passing through the Syrian Desert. It is recorded that his soldiers marched for two days without a single drop of water, before reaching a predetermined water source at an oasis. Khalid thus entered Northern Syria and caught the Byzantines on their right flank. According to modern historians, this ingenious strategic maneuver unhinged the Byzantine defences in Syria.

Battle of al-Qaryatayn was a minor battle between the Ghassanid Arab allies of the Byzantine empire, and the Rashidun Caliphate army. It was fought after Khalid ibn Walid had conquered Tadmur in Syria. His army marched to al-Qaryatayn, the inhabitants of which resisted the Muslims. They were fought, defeated and plundered.

Abu Ubaida ibn al-Jarrah, the supreme commander of the Muslim armies in Syria, had ordered Shurhabil ibn Hasana to attack Bosra. The latter laid siege to Bosra with his small army of 4000. The Roman and Ghassanid Arab garrison, realizing that this might be the advance guard of the larger Muslim army to come, sallied out of the fortified city and attacked Shurhabil, surrounding him from all sides; however, Khalid reached the arena with his cavalry and saved Shurhabil. The combined forces of Khalid, Shurhabil, and Abu Ubaidah then resumed the siege of Bosra, which surrendered some time in mid-July 634 CE, effectively ending the Ghassanid Dynasty.

Here Khalid took over the command of the Muslim armies in Syria from Abu Ubaidah, according to the instructions of the Caliph.

The Battle of Ajnadayn was fought in July or August 634, in a location close to Beit Guvrin in present-day Israel; it was the first major pitched battle between the Byzantine (Roman) Empire and the army of the Arab Rashidun Caliphate. The result of the battle was a decisive Muslim victory. The details of this battle are mostly known through Muslim sources, such as the ninth-century historian al-Waqidi.

The Battle of Yaqusa was a battle fought between the Byzantine and Rashidun armies. The Byzantine army was sent to delay the advance of the Arab army heading towards Damascus.

The Battle of Marj al-Saffar took place in 634. At Damascus, Thomas, son-in-law of Byzantine Emperor Heraclius, was in charge. Receiving the intelligence of Khalid's march towards Damascus he prepared the defences of Damascus. He wrote to Emperor Heraclius for reinforcement, who was at Emesa that time. Moreover, Thomas, in order to get more time to prepare for a siege, sent the armies to delay, or if possible, halt Khalid's march to Damascus. One such army was defeated at the Battle of Yaqusa in mid-August 634 near Lake Tiberias 150 km from Damascus, another army that halted the Muslim advance to Damascus was defeated in the Battle of Marj al-Saffar on 19 August 634. It is said that Umm Hakim, a Muslim heroine was involved in this battle and killed seven Byzantine soldiers.

After winning the Battle of Ajnadayn, the Muslim armies marched north and laid siege to Damascus.

To isolate the city from the rest of the region Khalid placed detachments south on the road to Palestine and in the north at the Damascus-Emesa route, and several other smaller detachments on routes towards Damascus. Heraclius' reinforcements were intercepted and routed at the;Battle of Sanita-al-Uqab, 30 kilometres (20;mi) from Damascus. Khalid's forces withstood three Roman sallies that tried to break the siege.

The city was taken after a monophysite bishop informed Khalid ibn al-Walid, the Muslim commander in chief, that it was possible to breach city walls by attacking a position only lightly defended at night. While Khalid entered the city by assault from the Eastern gate, Thomas, commander of the Byzantine garrison, negotiated a peaceful surrender at the Jabiyah gate with Abu Ubaidah, Khalid's second in command. After the surrender of the city, the commanders disputed the terms of the peace agreement.

Damascus was the first major city of the Eastern Roman Empire to fall in the Muslim conquest of Syria.

On 22 August, Abu Bakr, the first caliph, died, having made Umar his successor. Umar's first move was to relieve Khalid from command and appoint Abu Ubaidah ibn al-Jarrah as the new commander-in-chief of the Islamic army. Khalid pledged his loyalty to the new Caliph and continued to serve as an ordinary commander under Abu Ubaidah. He is reported to have said, "If Abu Bakr is dead and Umar is Caliph, then we listen and obey."

Abu Ubaidah moved more slowly and steadily, which had a concomitant effect on military operations in Syria. Abu Ubaidah, being an admirer of Khalid, made him commander of the cavalry and relied heavily on his advice during the whole campaign.

The Battle of Sanita-al-Uqab was fought in 634 between forces of the Rashidun Caliphate led by Khalid ibn al-Walid against a Byzantine force sent by Byzantine Emperor Heraclius to relieve the besieged garrison of Damascus. Leading up to the battle, the Caliphate forces had intended to isolate the city of Damascus from the rest of the region; Khalid placed detachments in the south on the road to Palestine and in the north on the Damascus-Emesa route, and several other smaller detachments on routes towards Damascus. These detachments were to act as scouts and as delaying forces against Byzantine reinforcements. Heraclius's reinforcements were intercepted, and though they initially gained the upper hand, were routed at the al Uqab (Eagle) Pass when Khalid personally arrived with reinforcements.

Battle of Marj-ud-Debaj was fought between the Byzantine army, survivors from the conquest of Damascus, and the Rashidun Caliphate army in September 634. It was a successful raid after three days of armistice, on the Byzantine survivors of the conquest of Damascus.

The Battle of Fahl was a major battle in the Muslim conquest of Byzantine Syria fought by the Arab troops of the nascent Islamic caliphate and Byzantine forces at or near Pella (Fahl) and nearby Scythopolis (Beisan), both in the Jordan Valley, in December 634 or January 635. Byzantine troops smarting from their rout by the Muslims at the battle of Ajnadayn or the Yarmuk had regrouped in Pella or Scythopolis and the Muslims pursued them there. The Muslim cavalry faced difficulty traversing over the muddied grounds around Beisan as the Byzantines cut irrigation ditches to flood the area and stave off the Muslim advance. The Muslims ultimately defeated the Byzantines, who are held to have suffered enormous casualties. Pella was subsequently captured, while Beisan and nearby Tiberias capitulated after short sieges by detachments of Muslim troops.

After Byzantine forces are destroyed in Battle of Fahl by Khalid, Rashidun army split their forces to continue the conquest in separate ways. Amr ibn al-Aas and Shurhabil ibn Hasana moved south to capture Palestine, while Abu Ubaidah and Khalid moved north to capture Northern Syria. While the Abu Ubaydah and Khalid were occupied at Fahl, leaving only Yazid ibn Abi Sufyan in Damascus. Heraclius sensing the opportunity to relieve Damascus and immediately sent an army under General Theodore the Patrician to recapture Damascus. Theodore brough a sizable forces of cavalry in this mission. Meanwhile, the caliphate army manage to learn Theodore movements as Abu Ubaydah and Khalid have already defeated the Byzantine in Fahl, they immediately taking a detour to intercept Theodore.

The battle actually consisted of two different battles in separate areas. But since the second battle was attended immediately by Khalid ibn Walid after he has finished the first battle in short span, early Muslim historians regard this conflicts as single conflict.

Rashidun army achieved decisive victory in this battle and all of the Byzantine commander are killed in both battles

The siege of Emesa was laid by the forces of Rashidun Caliphate from December 635 up until March 636. This led to the Islamic conquest of Emesa, which was a major trading city of the Byzantine Empire in the Levant.

The Battle of the Yarmuk was a major battle between the army of the Byzantine Empire and the Muslim forces of the Rashidun Caliphate. The battle consisted of a series of engagements that lasted for six days in August 636, near the Yarmouk River, along what are now the borders of Syria–Jordan and Syria–Israel, southeast of the Sea of Galilee. The result of the battle was a complete Muslim victory that ended Byzantine rule in Syria.

The Battle of the Yarmuk is regarded as one of the most decisive battles in military history, and it marked the first great wave of early Muslim conquests after the death of the Islamic prophet Muhammad, heralding the rapid advance of Islam into the then-Christian Levant.

To check the Arab advance and to recover lost territory, Emperor Heraclius had sent a massive expedition to the Levant in May 636. As the Byzantine army approached, the Arabs tactically withdrew from Syria and regrouped all their forces at the Yarmuk plains close to the Arabian Peninsula, where they were reinforced, and defeated the numerically superior Byzantine army.

The battle is widely regarded to be Khalid ibn al-Walid's greatest military victory and cemented his reputation as one of the greatest tacticians and cavalry commanders in history.

With the Byzantine army routed, the Muslims quickly recaptured the territory they had conquered prior to Yarmouk. Abu Ubaida held a meeting with his high commanders, including Khalid, and decided to conquer Jerusalem. The Siege of Jerusalem lasted four-six months, after which the city agreed to surrender, but only to Umar personally.

According to tradition, in 637 or 638, Caliph Umar traveled to Jerusalem in person to receive the submission of the city. The Patriarch thus surrendered to him.

With Emesa already in hand, Abu Ubaidah and Khalid moved towards Chalcis, which was strategically the most significant Byzantine fort. Through Chalcis the Byzantines would be able to guard Anatolia, Heraclius' homeland of Armenia, and the regional capital, Antioch. Abu Ubaidah sent Khalid with his mobile guard towards Chalcis. The virtually impregnable fort was guarded by Greek troops under Menas, reportedly second in prestige only to the Emperor himself. Menas, diverting from conventional Byzantine tactics, decided to face Khalid and destroy the leading elements of Muslim army before the main body could join them at Hazir 5 kilometres east of Chalcis.

The battle was still in its early stages when Menas was killed. As the news of his death spread among his men, the Byzantine soldiers went wild with fury and savagely attacked to avenge their leader's death. Khalid took a cavalry regiment and maneuvered from the side of one of the wings to attack the Byzantine army from the rear. Soon the entire Roman army was encircled and defeated. It is said that Menas and his garrison had never suffered such a severe defeat.

The resulting Battle of Hazir even reportedly forced Umar to praise Khalid's military genius, saying, "Khalid is truly the commander. May Allah have mercy upon Abu Bakr. He was a better judge of men than I have been.

Abu Ubaidah soon joined Khalid at Chalcis, which surrendered some time in June. With this strategic victory, the territory north of Chalcis lay open to the Muslims. Khalid and Abu Ubaidah continued their march northward and laid;siege to Aleppo, which was captured after fierce resistance from desperate Byzantine troops in October.;

Before marching towards Antioch, Khalid and Abu Ubaidah decided to isolate the city from Anatolia. They accordingly sent detachments north to eliminate all possible Byzantine forces and captured the garrison town of;Azaz, 50 kilometres from Aleppo; from there Muslims attacked Antioch from the eastern side, resulting in the;Battle of Iron bridge.

The Byzantine army, composed of the survivors of Yarmouk and other Syrian campaigns, was defeated, retreating to Antioch, whereupon the Muslims besieged the city. Having little hope of help from the Emperor, Antioch surrendered on 30 October, on the condition that all Byzantine troops would be given safe passage to Constantinople.;

After the devastating defeat in the Battle of Yarmouk, the remainder of the Byzantine Empire was left vulnerable. With few military resources left, it was no longer in a position to attempt a military comeback in Syria. To gain time to prepare a defense of the rest of his empire, Heraclius needed the Muslims occupied in Syria. Heraclius thus sought help from the Christian Arab tribes which came of Jazirah which particularly came from two cities along the Euphrates river, Circesium and Hīt. The tribes mustered a large army and marched against Emesa in no time, which was erected as military headquarter by Abu Ubaydah at the time.

When the Christian Arabs received the news of the arrival of fresh reinforcements led by the caliph himself, combined with Iyadh invasions of their homeland in Jazira, they immediately abandoned the siege and hastily withdrew there. By the time the Christian Arab coalitions leave, Khalid and his mobile guard has been reinforced by 4000 soldiers under Qa'qa from Iraq, and now has been given permission by Abu Ubaydah to came out of the fort to pursue the enemy. Khalid inflicted heavy losses to the Arab Christian coalition forces, which not only broke the entire siege, but also prevented them to return to Jazira.

The success of the defense, which not only repelled the siege attempt by the Byzantine allies but also allowed Iyadh to capture almost entire Jazira region, has motivated the caliphate to launch the full-scale invasion further to the north until it reached Armenia.

On the orders of Umar, Sa'd ibn Abi Waqqas, commander of the Muslim army in Iraq, sent an army under Iyad ibn Ghanm to conquer the region between the Tigris and the Euphrates up to Urfa. In 639–640, Raqqa fell into Muslim hands, followed by most of Jazirah, the last base of the Eastern Roman Empire in the region, which surrendered peacefully and agreed to pay Jizya.

The conquest of Jazirah was completed by 640 CE, after which Abu Ubaidah sent Khalid and Iyad ibn Ghanm (conqueror of Jazirah) to invade Byzantine territory north of there. They marched independently and captured Edessa, Amida, Malatya and the whole of Armenia up to Ararat and raided northern and central Anatolia. Heraclius had already abandoned all the forts between Antioch and Tartus to create a buffer zone between the Muslim controlled areas and Anatolia.

Umar then called a halt to the expedition and ordered Abu Ubaidah, now governor of Syria, to consolidate his rule there. This decision can be explained by the dismissal of Khalid from the army, which ended his military career, and a drought followed by a plague the year after.