Mowbray was the son of John 4th Lord Mowbray, and Elizabeth, Baroness Segrave. She was the daughter of John 4th Lord Segrave and Margaret, Countess of Norfolk, who was a daughter of Thomas of Brotherton, Earl of Norfolk[?], a son of [[Edward I of England | Edward I]. Thus Mowbray was the great-great-grandson of Edward I.
He succeeded his brother John as 6th Lord Mowbray and 7th Lord Segrave in 1382, and soon afterwards was created Earl of Nottingham, a title his elder brother had also held. Three years later he was appointed Earl Marshall, and in that capacity he fought against the Scots, and then against the French.
Mowbray was one of the Lords Appellant to Richard II[?], who deposed some of Richard's court favorites (1387). The king's uncle Thomas of Woodstock was imprisoned at Calais, where Mowbray was Captain. When Thomas was killed in 1397, it was probably at the king's orders and probably with Mowbray's involvement. A few weeks later he was created 1st Duke of Norfolk, though his aged grandmother the Countess of Norfolk was still alive. When she died the next year he also became 3rd Earl of Norfolk.
Later in the year (1389) Mowbray quarrelled with Henry Bolingbroke, Duke of Hereford (later Henry IV), apparently due to mutual suspicions stemming from their roles in the conspiracy against Thomas of Woodstock. The king banished them both. After Henry returned and usurped the throne, Mowbray was stripped of his dukedom, though he retained his other titles. He died of the plague in Venice, 22 September 1399.
Mowbray had no children by his first wife, Elizabeth, daughter and heiress of the 1st Baron Strange. He had two sons by his second wife, Elizabeth, daughter of the 4th Earl of Arundel: Thomas, 4th Earl of Norfolk; and John, 5th Earl and later 2nd Duke of Norfolk.