According to the Anglo-Saxon Chronicle he was eighty years old at his death, but the energy of his administration and the evidence with regard to the ages of his children and relatives render it almost impossible. In 628 the Chronicle records a battle between him and the West Saxons at Cirencester in that year. In 633 Penda and Ceadwalla overthrew Edwin at Hatfield Chase; but after the defeat of the Welsh king at Oswald at "Hefenfeith" in 644, Mercia seems to have been for a time subject to Northumbria.
In 642 Penda slew Oswald at a place called Maserfeld. He was continually raiding Northumbria and once almost succeeded in reducing Bamborough. He drove Cenwalh of Wessex, who had divorced Penda's sister, from his throne. In 654 he attacked the East Angles, and slew their king Anna of East Anglia. In 654 or 655 he invaded Northumbria in spite of the attempts of Oswiu to buy him off, and was defeated and slain on the banks of the Winwaed. In the reign of Penda the districts corresponding to Cheshire, Shropshire and Herefordshire were probably acquired, and he established his son Peada as a dependent prince in Middle Anglia. Although a pagan, he allowed his daughter Cyneburg to marry Ecgfrith, the son of Oswiu, and it was in his reign, via Peada, that Christianity was introduced into Middle Anglia.