Born to a working-class Irish migrant family in Tranmere, Cheshire, O'Grady moved to London in the late 1970s, initially working as a peripatetic care officer for Camden Council.

[17] Leaving school aged 16, O'Grady obtained a job in the civil service, working as a clerical assistant for the DHSS at their Liverpool office; he commuted in from his parents' Tranmere home.

[21] He also had casual sex with a female friend, Diane Jansen,[23] who became pregnant, news which O'Grady discovered in the same week that both his parents suffered heart attacks; his mother made a recovery, but his father died.

[26] Realising this wage was insufficient to support both himself and his daughter, he travelled to London, lodging in Westbourne Green, but found only poorly paid work as a barman.

[28][29] Returning to London, he rented a flat in Crouch End and began busking with a friend in Camden Town before obtaining a job as a physiotherapist's assistant at the Royal Northern Hospital.

[30] Made redundant by public sector cuts, O'Grady took up a job at a gay club called the Showplace, befriending a Portuguese lesbian named Teresa Fernandes.

While working for Camden Social Services, O'Grady made his first attempt at putting together a drag act, creating the character of Lily Savage; he later said, "I wanted to get up there but be larger than life, a creature that was more cartoon than human.

"[36] His debut was on the afternoon of 7 October 1978 at The Black Cap gay pub in Camden, where his act involved miming the words to Barbra Streisand's "Nobody Makes a Pass at Me" from the show Pins and Needles.

[44] Amid mass unemployment, O'Grady briefly lived off the dole before resurrecting the Playgirls with his friend Vera; initially performing in Liverpool, where they were caught up in the 1981 Toxteth riots, they began touring other parts of northern England until returning to London.

[45] Again working as a support worker for Camden Council Social Services,[46] O'Grady lived in Vauxhall and then Brixton before reviving the Playgirls with Hush, devising an act based upon the film What Ever Happened to Baby Jane?

[49] The Playgirls gained bookings to appear across London, and also in Amsterdam and Copenhagen; O'Grady and Hush joined with drag artist David Dale to form an act known as "LSD", which stood for "Lily, Sandra, and Doris".

[52] After six months, he transferred his act to the nearby Royal Vauxhall Tavern (RVT) gay pub, re-opening his show on Thursday nights as "Stars of the Future".

[76] O'Grady obtained his breakthrough into television when he played the character of a transvestite prostitute informant, Roxanne, in three episodes of ITV's police drama The Bill between 1988 and 1990.

[93] Given top billing at the gay rights charity Stonewall's 1994 Equality Show in Albert Hall,[94] he also played the role of Nancy in the London Palladium's performance of the musical Oliver!.

"[97] After Paula Yates resigned as presenter of the Channel 4 morning television program The Big Breakfast, its production company Planet 24 employed O'Grady to replace her.

[100] O'Grady found the early morning starts difficult, particularly as he was also appearing as Lily in a musical version of Prisoner Cell Block H at the Queen's Theatre in London's West End.

"[104] At the time, O'Grady had been making greater attempts to get to know his teenage daughter; the Daily Mirror tabloid treated her existence as a headline scandal in autumn 1994.

[107] He turned down ITV's subsequent offer of a weekly show because it would air before the watershed and thus force him to drastically alter his act into a form of light entertainment.

[114] In 1998, the BBC produced a six-week Sunday series titled The Lily Savage Show, during which he interviewed guests like Elton John, Alan Yentob, and Anthea Turner.

[125] With increased earnings—his assets were estimated to total £4 million[126]—in 1999 O'Grady purchased a house in Aldington, Kent from comedian Vic Reeves, decorating it in an art nouveau style and establishing a smallholding.

Although poorly received by the tabloid press, it achieved good ratings, and ITV commissioned a second series, Paul O'Grady's America, in which he visited various U.S. cities.

[137] Although turning down most offers to appear in a sitcom, he agreed to play the manager of a Merseyside bingo hall in the BBC series Eyes Down, commenting: "He's an evil, twisted man who hates everything that moves.

[144] There was initial press concern that O'Grady's style of adult humour would not be appropriate for a daytime slot, but ITV's controller of entertainment, Mark Wells, declared that "Paul is one of the funniest people on television – he deserves to be on it far more than he is.

[159] Press accused O'Grady of moving in pursuit of a higher salary;[160] Channel 4 offered him a contract for £2 million a year, making him one of Britain's highest-paid television stars.

[177] In October, O'Grady attracted media attention after calling the Conservative–Liberal Democrat coalition government "bastards" on his show for mass cuts to social services.

[179] Paul O'Grady Live was picked up for a second series from April to July 2011, and included a special devoted to American pop star Lady Gaga.

[241] A final series of For The Love of Dogs that O'Grady recorded in summer 2022 aired from April to September 2023 on ITV, and on 30 January 2024, it was announced that the show would continue with a new presenter, Alison Hammond.

[259] O'Grady divided his time between his Central London flat and his rural Kentish farmhouse,[260] where he grew organic fruit and vegetables[261] and a variety of herbs, having a keen interest in herbal medicine.

[262] A lifelong animal lover,[104] as a child O'Grady kept rabbits, hamsters, guinea pigs, mice, a ferret and a rat as pets; he commented that his mother thought him "a bit weird" as a result.

[276] His death was announced by his husband, André Portasio,[277] and tributes poured in from global figures and celebrities, including from Queen Camilla, television presenter Lorraine Kelly and LGBT rights campaigner Peter Tatchell.