Alexander's legacy extended beyond his military conquests, and his reign marked a turning point in European and Asian history. His campaigns greatly increased contacts and trade between East and West, and vast areas to the east were significantly exposed to Greek civilization and influence.

Alexander's most immediate legacy was the introduction of Macedonian rule to huge new swathes of Asia. At the time of his death, Alexander's empire covered some 5,200,000 km2 (2,000,000 sq mi), and was the largest state of its time. Many of these areas remained in Macedonian hands or under Greek influence for the next 200–300 years. The successor states that emerged were, at least initially, dominant forces, and these 300 years are often referred to as the Hellenistic period.

The eastern borders of Alexander's empire began to collapse even during his lifetime. However, the power vacuum he left in the northwest of the Indian subcontinent directly gave rise to one of the most powerful Indian dynasties in history, the Maurya Empire.

Alexander and his exploits were admired by many Romans, especially generals, who wanted to associate themselves with his achievements. Polybius began his Histories by reminding Romans of Alexander's achievements, and thereafter Roman leaders saw him as a role model. Pompey the Great adopted the epithet "Magnus" and even Alexander's anastole-type haircut, and searched the conquered lands of the east for Alexander's 260-year-old cloak, which he then wore as a sign of greatness. Julius Caesar dedicated a Lysippean equestrian bronze statue but replaced Alexander's head with his own, while Octavian visited Alexander's tomb in Alexandria and temporarily changed his seal from a sphinx to Alexander's profile.