Upon the death of Philip, the last Duke of Burgundy of the old race, in November 1361, Edward III, desirous of securing to his family the splendid patrimony of the widow, Margaret of Flanders, commissioned the Bishop of Winchester and others, on 8th February following, to make overtures for a marriage between Edmund of Langley and the Duchess; but, although the alliance had the approbation of her father, Count Louis, its accomplishment was frustrated by the King of France who influenced the Pope to withhold the necessary dispensation.

Edmund was created Earl of Cambridge on 13th November 1362. In 1369, the Earls of Cambridge and Pembroke were sent with reinforcements to the army of the Black Prince in Aquitaine and, having landed at St. Malo, were received at Nantes, with great rejoicings, by their brother-in-law, the Duke of Brittany. He conducted them through his territories into Poitou without the expected molestation from the hostile occupants of a large portion of the Duchy. On their arrival at Angoulême, where the Prince and Princess of Wales then kept their Court, they were ordered, with a detachment of three thousand men, to make an incursion into Perigord. Bourdeille, one of the strong boroughs of that county, situated on the River Drome, was then taken, after a siege of nine weeks, and a most gallant resistance of the garrison. The attention of the two earls was next directed towards Roche-sur-Yon in Poitou, which also fell into their power.

The castle of Belle Perche, in the Bourbonnois, had been seized by the English and in it, Isabel of Valois, Duchess of Bourbon, half-sister of King Philip VI. When siege was laid to the place by Louis, Duke of Bourbon, her son, Cambridge and Pembroke soon hastened to its relief. After having ineffectually challenged the Duke to choose a position in which to give them battle, Chandos' Herald was commanded to inform him that, on a day within the three following, he might, at the hour of noon, see his lady-mother issue, under convoy, from the fort and that he might rescue her if he should think fit to attempt it. The Duke, reproaching the earls for their want of chivalrous respect towards an aging princess, declined the proposed rescue, expressing, at the same time, his firm resolve to obtain possession of the castle at all hazards. On the day and at the hour fixed upon, at the sound of a trumpet, John Montacute, nephew of the Earl of Salisbury, was observed marching out of the fort at the head of the garrison, in order of battle, the minstrels playing and banners and pennons flying. In the midst, the Duchess of Bourbon, mounted on a superbly caparisoned palfrey and surrounded by her ladies and damsels. Having delivered the fair captives into the charge of Sir Eustace D'Abridgecourt and Sir John Devereux, the escort retired in the same order within the English lines, abandoning the castle of Belle Perche to the Duke of Bourbon.

Cambridge was with the Prince of Wales at the capture and merciless sacking of the town of Limoges and the Black Prince, having soon afterwards in January 1371, lost, by death, his first-born son, Edward, at Bordeaux, departed from thence for England. He was accompanied by his brothers, Lancaster and Cambridge, who were immediately ordered to return into Gascony.

In 1372, Edmund married the Princess Isabel of Castile & Leon, the youngest of the two daughters of King Pedro "the Cruel". In the same year, he was still engaged in warlike operations in France, but, before the conclusion of it, was again in England. On the 18th November 1374, he embarked at Southampton as commander of an expedition to Brittany; but upon the truce concluded at Bruges by the Dukes of Burgundy and Lancaster on 27th June following, Cambridge, as well as the Duke and Duchess of Brittany, again returned to England. The truce expiring in April 1377 and, soon after the death of Edward Ill, the French effected several landings on the English coast. Cambridge proceeded with a considerable force to Dover Castle, of which he had been appointed constable on the 12th July 1376. In 1378, Lancaster and Cambridge passed with an army into Normandy, but without accomplishing any material object. Although the King of Navarre had put them in possession of Cherbourg.

In 1381, Cambridge, at the head of an expedition to Portugal, then at war with Castile, was joyfully received at Lisbon by King Ferdinand, who affianced his daughter Beatrice to Edward, the Earl's son. However, on the conclusion of peace between the belligerents in the following year, the English quitted Portugal and the Princess Beatrice was, soon afterwards, given in marriage to the son of the King of Castile.

The Earl was in the expedition against Scotland in 1385 and, upon the King's return, was created Duke of York on 6th August in that year. When Richard II went to Ireland in 1394, the Duke was appointed guardian of the realm during his absence.

Upon the accession of the House of Lancaster, the Duke of York absented himself from Court and remained in retirement at his palace in Langley, where he died on the 1st August 1402. By his will, dated 25th November 1400, he directed his interment in the Church of the Friary of Langley, near the remains of Isabel, his first consort, who had died in 1394. His tomb of alabaster and black marble, richly sculptured and adorned with shields of arms, was, at the dissolution of the Friary, removed into the north-east corner of the chancel of the parish church of Langley, where it is still extant.

By Isabel of Castile, the Duke of York had two sons and one daughter: Edward, who succeeded him, and died, without issue, in 1415; Richard, Earl of Cambridge; and Constance, wife of Thomas Le Despenser, Earl of Gloucester.

By Joan Holland, his second wife, daughter of Thomas, Earl of Kent, he left no issue.