Edmund was son of Roger Mortimer, 4th Earl of March by Alianore de Holland, daughter of Thomas Holland, 2nd Earl of Kent and Alice Fitzalan. Alice was daughter to Richard Fitzalan, 10th Earl of Arundel and Eleanor of Lancaster.
On his father's side, Edmund was a direct descendant of Edward III of England through Edward's second surviving son, Lionel of Antwerp. Because the senior line of succession through King Richard II had no issue, Edmund's father, Roger Mortimer, was next in line for the throne and was accordingly named heir presumptive in 1385.
On September 30, 1399 Richard was deposed and the crown usurped by Henry of Lancaster. The young Earl of March and his brother Roger were then kept in custody by Henry IV, who, however, treated them honourably.
Regarded as the Yorkist Pretender by Bolingbroke and the Lancastrians, his claim was in fact superior to Bolingbroke, and his children and descendants would carry the banner for the Yorkists.
Their captivity briefly ended in March, 1405, when Edmund was 14 years old, when they were carried off from Windsor Castle by the opponents of the House of Lancaster, on the orders of Constance of York. Their uncle, Sir Edmund Mortimer, and his brother-in-law Henry Percy (Hotspur) were leaders in league with Owain Glyndŵr. The boys were soon recaptured, and in 1409 were committed to the care of Henry of Monmouth, Prince of Wales.
He continued to enjoy the favour of the King in spite of the Southampton Plot in 1415 to place Mortimer on the throne, in which his brother-in-law and cousin, Richard, Earl of Cambridge, played the leading part. Mortimer was reportedly approached by the conspirators at a very late stage in the preparations, and after a period of about ten days informed the King of the threat against him. Cambridge was attainted as a result and executed for treason.
Thereafter, March accompanied Henry V to France in several campaigns of the Hundred Years' War. He did not fight at Agincourt, being ill at the time, but did participate in the conquest of Normandy and the other campaigns that lead up to the signing of the Treaty of Troyes. When Henry V died on August 31, 1422 and was succeeded by his one-year-old son Henry VI of England, Mortimer became a member of the Council of Regency.
March was appointed lieutenant of Ireland in May of 1423 (a post also held by his father and grandfather). He worked through a deputy at first, but in February 1424 he took ship for Ireland.
Mortimer died in Ireland of the plague in 1425 and was buried at Clare Priory, Suffolk. He married Anne Stafford, daughter of Edmund Stafford, 5th Earl of Stafford, but he left no issue. The Earldom of March, the Earldom of Ulster and his estates therefore passed to his nephew, Anne Mortimer's son, Richard Plantagenet (later restored as 3rd Duke of York, who was nevertheless styled "Earl of March", as was his son). On Richard's son's accession to the throne in 1461 as King Edward IV, the earldoms merged into the Crown.