He was born on 25 February 1475, at Warwick, the family home of his mother, the Duchess of Clarence, formerly Lady Isabella Neville, elder daughter of the 16th Earl of Warwick ("Warwick the Kingmaker"). He was created Earl of Warwick in 1478, shortly after the attainder and execution of his father for treason. His potential claim to the throne following the deposition of his cousin, King Edward V, in 1483, was overlooked because of the argument that the attainder of his father also barred Warwick from the succession (although that could have been reversed by an Act of Parliament).
After the death of King Richard's son, the Prince of Wales, in 1484, the 10-year-old Warwick was named heir to the throne, possibly thanks to the influence of Queen Anne, his aunt, who had adopted him and his sister Margaret following their parents' deaths. However, as soon as the Queen died, the King named his sister Elizabeth's son, the adult Earl of Lincoln, his heir in place of Warwick. As the American historian Paul Murray Kendall put it (in 1955), "Warwick . . . appears to have been what in the present age would be called a retarded child." British historian Jeremy Potter mentioned (in 1983) some of the contemporary evidence upon which historians based that conclusion: "Warwick . . . may have been simple-minded: later he was said not to be able to tell a goose from a capon." King Richard is believed to have named him his heir as a temporary measure only to please his dying queen, who survived her own son's death by less than a year.
After King Richard's death in 1485, Warwick was kept a prisoner by Henry VII because his claim, albeit tarnished, could become a threat to the new King, particularly after the appearance of the pretender Lambert Simnel in 1487. Although, in 1490, he was confirmed in his title of Earl of Warwick despite his father's attainder, he remained in the Tower of London until the arrival of another pretender, Perkin Warbeck, in 1499. A supposed plot to escape between the two resulted in Warbeck's hanging and Warwick's beheading, both for treason.
Upon his death, the House of Plantagenet became extinct in the male line.