As he approached his sixties, Waugh was in poor health, prematurely aged, "fat, deaf, short of breath", according to Patey.His biographer Martin Stannard likened his appearance around this time to that of "an exhausted rogue jollied up by drink". In 1962 Waugh began work on his autobiography, and that same year wrote his final fiction, the long short story Basil Seal Rides Again. This revival of the protagonist of Black Mischief and Put Out More Flags was published in 1963; the Times Literary Supplement called it a "nasty little book". When the first volume of autobiography, A Little Learning, was published in 1964, Waugh's often oblique tone and discreet name changes ensured that friends avoided the embarrassments that some had feared.
Waugh had welcomed the accession in 1958 of Pope John XXIII and wrote an appreciative tribute on the pope's death in 1963. However, he became increasingly concerned by the decisions emerging from the Second Vatican Council, which was convened by Pope John in October 1962 and continued under his successor, Paul VI until 1965. Waugh, a staunch opponent of Church reform, was particularly distressed by the replacement of the universal Latin Mass with the vernacular. In a Spectator article of 23 November 1962, he argued the case against change in a manner described by a later commentator as "sharp-edged reasonableness". He wrote to Nancy Mitford that "the buggering up of the Church is a deep sorrow to me.... We write letters to the paper. A fat lot of good that does."
In 1965, a new financial crisis arose from an apparent flaw in the terms of the "Save the Children" trust, and a large sum of back tax was being demanded. Waugh's agent, A.D. Peters, negotiated a settlement with the tax authorities for a manageable amount, but in his concern to generate funds, Waugh signed contracts to write several books, including a history of the papacy, an illustrated book on the Crusades and a second volume of autobiography. Waugh's physical and mental deterioration prevented any work on these projects, and the contracts were cancelled. He described himself as "toothless, deaf, melancholic, shaky on my pins, unable to eat, full of dope, quite idle" and expressed the belief that "all fates were worse than death". His only significant literary activity in 1965 was the editing of the three war novels into a single volume, published as Sword of Honour.
On Easter Day, 10 April 1966, after attending a Latin Mass in a neighbouring village with members of his family, Waugh died of heart failure at his Combe Florey home, at 62. He was buried, by special arrangement, in a consecrated plot outside the Anglican churchyard of the Church of St Peter & St Paul, Combe Florey. A Requiem Mass, in Latin, was celebrated in Westminster Cathedral on 21 April 1966.