It was pagan Mercian king Penda, 626/633-655AD, who freely allowed Christian missionaries from Lindisfarne into Mercia. After a reign of successful battles against all his opponents, Penda was defeated and killed at the Battle of Winwaed by the Northumbrian king Oswiu in 655. This battle led to a temporary collapse of Mercian power. After the murder of Penda's son Peada, Oswiu assumed control of the whole of Mercia. Another son of Penda, Wulfhere, 658-675AD, successfully restored the power of Mercia, and he ruled until 675, but the end of his reign saw defeat against Northumbria.

The next important king of Mercia was Æthelbald 716-757AD who, because of his prowess as a military leader, acquired the title of Bretwalda. At the beginning of his reign he had to face two strong rival kings, Wihtred of Kent and Ine of Wessex. But when Wihtred died in 725, and Ine abdicated his throne the next year to become a monk in Rome, Æthelbald was free to establish Mercia's supremacy over the rest of the Anglo-Saxons south of the Humber.

After Æthelbald was murdered by one of his bodyguards in 757 a civil war followed which came to an end with the victory of Offa who went on became the one of the greatest kings of Mercia. He won battles and dominated southern England, and took an active part in administering the affairs of his kingdom. He founded market towns and oversaw the first major issues of gold coins in Britain. He also assumed a role in the administration of the church in England and sponsored the archbishopric of Lichfield. Offa is also credited with the construction of Offa's Dyke which marked the border between Wales and Mercia. Offa died in 796.

In 868 Viking invaders from Denmark occupied Nottingham. The last king of Mercia, Burgred, was ousted from his kingdom by Vikings in 874. In 886, the eastern part of the kingdom became part of the Danelaw and Mercia was reduced to its western portion only. The Danes appointed a Mercian thegn, Ceolwulf II, as king and the remaining independent part of Mercia was ruled by Earl Æthelred of Mercia 883-911AD.

Æthelred married Æthelflæd, daughter of Alfred the Great of Wessex, and she gradually assumed power as Æthelred became increasingly ill. His illness may have been caused by wounds inflicted in battle against the Vikings at Tettenhall, where the last large Viking army to ravage England suffered defeat by the combined armies of Mercia and Wessex. In 911 after Æthelred’s death, Æthelflæd gave Oxford and London together with the lands belonging both, to her brother Edward the Elder of Wessex as a token of loyalty. She then fortified Mercia's existing borders and in 917 expelled the Danes from Derby, ruling alone as ‘Lady of the Mercians’ until her death in 918.

The Anglo-Saxon Chronicle details the end of Mercian independence following the death of Æthelflæd. Edward of Wessex took over the fortress at Tamworth and accepted the submission of all those who were settled in Mercia, both Danish and English. In 919 Ælfwynn, Æthelred's daughter, was deprived of any authority in Mercia and was taken to Wessex.

However references to Mercia continue in the annals during the reigns of Æthelstan and his successors. In 975 King Edgar is described as 'friend of the West Saxons and protector of the Mercians', and when Edgar 955-959AD became king of Mercia a separate political existence from Wessex was restored. This occurred again in 1016, when the kingdom was divided between Cnut and Edmund Ironside, with Cnut taking Mercia. In 1017 Cnut awarded the governance of Mercia to Eadric Streona.