Sykes was born in London, one of six children, and grew up in Sevenoaks, Kent. Among her friends at Ide Hill Church of England primary school was Rowan Pelling (b.1968), who became the editor (or "editrice") of the Erotic Review. From there she went to Sevenoaks School, an independent school founded in the 15th century, and then to Worcester College, Oxford in 1988, where she graduated in modern history.

Sykes' mother, Valerie Goad, a dress designer, separated from Sykes' father Mark while Plum was at Oxford. Her grandfather, Christopher Sykes (1907–1986), was a friend and official biographer (1975) of the novelist Evelyn Waugh and son of the diplomat Sir Mark Sykes, sixth baronet (1869–1919), associated with the so-called Sykes-Picot Agreement of 1916, by which Britain and France provided for the partition of the Ottoman empire after the end of the First World War. An 18th century forebear, the second baronet, Sir Christopher Sykes (1749-1801), was a major figure in the enclosure movement that transformed the appearance and management of the English countryside.

In 1993 Plum Sykes became a fashion assistant at British Vogue. She was featured that year, with, among others, designer Bella Freud and model Stella Tennant in Babes in London, in a photographic shoot by the American Steven Meisel (responsible in 1992 for the singer Madonna's controversial collection, Sex), which was produced by the rising fashion guru Isabella Blow (1958-2007).

In 1997 Sykes became a contributing editor on fashion for American Vogue, of which Anna Wintour, also British, had been editor-in-chief since 1988. She became a familiar figure on the New York social scene, being frequently described as an "It girl".

A decade later, at the age of 38, Sykes reflected that "when you hit 30 you lose your edge": invited by the Times to comment on the late-nineties trend for ultra-high heeled shoes, she observed that "these weird space-age shoes look cool and trendy and are a way of getting back to some degree", but that "this type of trend is not a classic version of beauty. Men want women to be sexy. They'd be happy if we were all [the model] Gisele Bündchen, but that's just not fashion" .

The world of New York fashion was the setting for Sykes' first novel, Bergdorf Blondes (2004), which was one of the most successful examples of "chick lit" (or "chic lit" as some dubbed Sykes' writing) and sold a quarter of a million copies worldwide. It took its title from the Bergdorf Goodman store in Upper Manhattan, founded at the end of the 19th century.

A second novel, The Debutante Divorcée, was published in 2006. Sykes publicised it with an array of personal appearances at stores in New York (Chanel, Ralph Lauren, Frederic Fekkai, Ferragamo, Neiman Marcus and Oscar de la Renta). The Debutante Divorcée appeared in paperback in 2007.

Some have seen Sykes' books as lying in natural succession to Sex and the City, Candace Bushnell's column in the New York Observer, which was the inspiration for a highly successful television series (HBO 1998–2004). However, despite their satire, others have regarded them as too rooted in Sykes' own Park Avenue "set" to be reflective more generally of women's lives in post-9/11 Manhattan. Anita Loos' Gentlemen Prefer Blondes (1925) is perhaps a closer, if incomparable, antecedent.

Plum Sykes married British entrepreneur Toby Rowland, son of businessman "Tiny" Rowland, at Sledmere House, her family's ancestral home (1751) in the East Riding of Yorkshire. Her dress was designed by her friend and protégé of Isabella Blow, Alexander McQueen (1969-2010), of whom Sykes was sometimes described as a muse. She modelled for some of McQueen's earliest catwalk shows, as well as for photoshoots of his designs. Sykes and Rowland had their first child, Ursula, in October 2006 and their second child, Tess, in June 2010.

Sykes' twin sister Lucy, who moved to New York in 1996, became fashion director of Marie Claire, and later a designer of children's clothes. In the late 1990s the Sykes sisters were sometimes described as the "twin set", Plum later joking, with reference to the heiresses Paris and Nicky Hilton, that "Lucy and I were Paris and Nicky without the sextape" (an allusion to a video recording of Paris Hilton and a former boyfriend that had been posted on the Internet in 2003). Lucy Sykes married Euan Rellie, a New York-based investment banker, in 2002.