After Caesar's expeditions, the Romans began a serious and sustained attempt to conquer Britain in CE 43, at the behest of Emperor Claudius. They landed in Kent with four legions and defeated two armies led by the kings of the Catuvellauni tribe, Caratacus and Togodumnus, in battles at the Medway and the Thames. The Catuvellauni held sway over most of the southeastern corner of England; eleven local rulers surrendered, a number of client kingdoms were established, and the rest became a Roman province with Camulodunum as its capital. Over the next four years, the territory was consolidated and the future emperor Vespasian led a campaign into the Southwest where he subjugated two more tribes. By CE 54 the border had been pushed back to the Severn and the Trent, and campaigns were underway to subjugate Northern England and Wales.

But in CE 60, under the leadership of the warrior-queen Boudicca, the tribes rebelled against the Romans. At first, the rebels had great success. They burned Camulodunum, Londinium and Verulamium (modern-day Colchester, London and St. Albans respectively) to the ground. The Second Legion Augusta, stationed at Exeter, refused to move for fear of revolt among the locals. Londinium governor Suetonius Paulinus evacuated the city before the rebels sacked and burned it. In the end, the rebels were said to have killed 70,000 Romans and Roman sympathisers. Paulinus gathered what was left of the Roman army. In the decisive battle, 10,000 Romans faced nearly 100,000 warriors somewhere along the line of Watling Street, at the end of which Boudicca was utterly defeated. It was said that 80,000 rebels were killed, with only 400 Roman casualties.

Over the next 20 years, the borders expanded slightly, but the governor Agricola incorporated into the province the last pockets of independence in Wales and Northern England. He also led a campaign into Scotland which was recalled by Emperor Domitian. The border gradually formed along the Stanegate road in Northern England, solidified by Hadrian's Wall built in CE 138, despite temporary forays into Scotland. The Romans and their culture stayed in charge for 350 years. Traces of their presence are ubiquitous throughout England.