Æthelfrith of Northumbria had in 592 succeeded Hussa as king of Bernicia.

His accession possibly involves dynastic rivalry and the exile of Hussa's relatives.

Æthelfrith protects his borders in 603 by fighting and defeating the Scots king of Dalriada (Argyll) and the Britons of Strathclyde at Degasaston (Dawson Rig, Liddesdale?).

With Æthelfrith’s defeat of the Scots and Britons at Degsastan in 603, Angles now dominate central Britain from east to west below the Firth of Forth.

Æthelfrith, king of Bernicia, gains control of Deira around 604; the circumstances of this are unknown.

That he gained Deira through conquest is suggested by the exile of Edwin, son of the former king Ælla, and Hereric, Edwin's nephew, who are both notable members of the Deiran royal line; the short five-year reign of Aethelric of Deira, who ruled immediately prior to Æthelfrith's acquisition of Deira, may also indicate conquest.

D. P. Kirby on the other hand suggested that Æthelfrith's rule of both kingdoms may have represented "a formalization of an existing relationship" of cooperation between the two.

Kirby also pointed out that Edwin did not necessarily go into exile immediately, and considered it likely that Æthelfrith's hostility towards him "manifested itself only by degrees".

It is also around 604 that Æthelfrith's son Oswald is born.

Oswald's mother is Acha, daughter of Ælla, and thus Edwin's sister.

Although Bede does not explicitly say Æthelfrith married Acha, it is thought that he did so; he may have married her prior to taking power in Deira, in which case the marriage may have facilitated it, or he may have done so afterwards in order to consolidate his position there.

Æthelfrith attacks the Kingdom of Powys later in his reign, probably between 613 and 616, and defeats its army in a battle at Chester, in which the Powysian king Selyf Sarffgadau is killed, along with another king called Cetula, who is probably Cadwal Crysban of Rhôs.

He also massacres the monks of Bangor-Is-Coed who had assembled to aid the Britons by their prayers.

Bede says that he decided to attack them because, although they were not armed, they were opposing him through their prayers.

The number of dead monks is said to be about twelve hundred, with only fifty escaping.

It has been suggested that Æthelfrith may have done this for tactical reasons, to catch the Britons by surprise and force them to change their plans in order to protect the monks.

Æthelfrith after first killing the monks prevails over the enemy army, although Bede notes that Æthelfrith's own forces suffered considerable loss.

Æthelfrith's victory at Chester has been seen as having great strategic importance, as it may have resulted in the separation of the Britons between those in Wales and those to the north; however, Stenton noted that Bede was mainly concerned with the massacre of the monks and does not indicate that he regarded the battle as a historical "turning-point.”

Koch says that the older view that the battle cut the two British areas off from each other is now "generally understood" to be outdated, as Æthelfrith died soon after, and there is "almost no archaeological evidence for Anglo-Saxon settlement within the pagan period in Cheshire or Lancashire,” and in any case the sea would have been the primary means of communication.

The Deiran exile Hereric had been poisoned while at the court of Ceretic, king of Elmet; Æthelfrith may have been responsible for this killing.

Edwin, apparently seeking safety from Æthelfrith, seems to have traveled between many different kingdoms during his period of exile.

He may have spent time during his exile in the British kingdom of Gwynedd, and it seems clear that he spent time in Mercia, because he married a daughter of king Cearl.

Edwin ended up in East Anglia, under the protection of its king, Raedwald.

Æthelfrith had sent messengers to bribe Raedwald with "a great sum of money" into killing Edwin; Bede reports that his first message had no effect, but Æthelfrith had sent more messengers and threatened war if Raedwald did not comply (bribes and threats of this kind may have previously been used to accomplish Hereric's killing.)

Raedwald had eventually agreed to kill Edwin or hand him over to Æthelfrith's messengers, but was reportedly dissuaded from this by his wife, who said that such a thing was unworthy of his honor.

Instead, Raedwald raises an army and marches against Æthelfrith, and around 616 Æthelfrith is defeated and killed on the east side of the River Idle by an army under Raedwald; Bede says that Æthelfrith had the inferior army, because Raedwald had not given him time to bring all his forces together.

While presented by Bede as being fought simply over the issue of Edwin, this war may have actually involved questions of power and territory between the two rulers.

Æthelfrith's heir, prince Eanfrith, seeks refuge with his mother's family, probably in Gododdin (modern Scotland) and moves further north into Pictland.

Æthelfrith's younger sons Oswald and Oswiu escape to the court of king Eochaid Buide of Dál Riata, where they are soon converted to Christianity by the monks of Iona.

Æthelfrith’s son Oswald, following the death of his father, moves to the Scottish island of Iona and is there converted to Christianity.