The son of artist-writers Clayton Knight and Katharine Sturges, Hilary Knight was born on Long Island in Hempstead. His father illustrated aviation books, and his mother was a fashion and book illustrator. Living in Roslyn, New York as a child, Hilary was age six when he moved to Manhattan with his family. Knight recalled:

As a child, I loved to look at a set of books which belonged to my mother. They were illustrated by Edmund Dulac in a romantic, wonderful, detailed manner. I know he has influenced my style.

After study with George Grosz and Reginald Marsh at the Art Students League, Knight labored as a ship painter while serving in the Navy from 1944 to 1946. Returning to New York, he studied architectural drafting (at Delahanty Institute), interior design and theatre design, working for one summer as an assistant designer at an Ogunquit, Maine theater. He painted murals in private homes and entered the field of magazine illustration, starting with Mademoiselle in 1952, followed by House & Garden, Gourmet, McCalls and Woman's Home Companion. His work as a humorous illustrator was strongly influenced by the British cartoonist Ronald Searle.

In 1955, he collaborated with Kay Thompson to create the whimsical black/white/pink look of Eloise. The live CBS television adaptation on Playhouse 90 (1956) with Evelyn Rudie as Eloise received such negative reviews that Kay Thompson vowed never to allow another film or TV adaptation.

Three book sequels followed: Eloise in Paris (1957), Eloise at Christmastime (1958) and Eloise in Moscow (1959). Thompson and Knight teamed to create another sequel, Eloise Takes a Bawth, working with children's book editor Ursula Nordstrom. That title was announced in the Harper Books for Boys and Girls fall 1964 catalog, but in the mid-1960s, Thompson removed the three Eloise sequels from print and did not allow Eloise Takes a Bawth to be published. It was an action that deprived her collaborator of income for decades (a situation that changed with Thompson's death in 1998). In Salon, Amy Benfer speculated on Thompson's motives in "Will the real Eloise please stand up?" (June 1, 1999):

Kay Thompson got sick of us. Our initial admiration—a mass consumption of all things Eloise—was viewed as imitation and she did not consider it a form of flattery. Adults and children flooded the Plaza, all insisting that they were Eloise... I think she became jealous. So does Hilary Knight, Thompson's illustrator and collaborator. His pink-splashed black and white drawings of the child Maurice Sendak called, "that brazen loose-limbed delicious little girl monster" provide the punch line to Thompson's allusive, scatting prose. Knight's contribution to a 1996 profile of Thompson in Vanity Fair is an illustration that shows Thompson kicking the chair out from under Eloise to scrawl "I am Eloise" in lipstick on the vanity mirror in the Plaza's powder room. Knight's illustration may seem a little tawdry. But then again, Knight himself got into something of a tangle with Ms. Thompson over the ownership of Eloise. Their professional relationship effectively ended when Thompson pulled from publication a nearly completed manuscript of yet another sequel; this one was entitled Eloise Takes a Bawth. In later years, Thompson refused to return Knight's phone calls. Kay Thompson's sense of possession was so strong that she became unwilling to share Eloise, even with the person who literally animated the child in her head.

Eloise Takes a Bawth was finally published in 2002. Knight recalled:

Kay and I were like parents to Eloise. We decided that we'd never make her older than six, and that we'd always keep the parents in the background. When you really study the book, you see that Eloise is somewhat wistful. And I guess my job now is to continue what Kay might have thought she was doing when she pulled the books in the first place—to protect Eloise.

Other publications with Knight illustrations include Good Housekeeping and the children's magazine, Cricket. In addition to creating children's picture books...among them, in collaboration with poet Margaret Fishback, A Child's Book of Natural History (USA: Platt & Monk, 1969), a revision and extension of A Child's Primer of Natural History by Oliver Herford...Knight has illustrated for other genres, such as Peg Bracken's The I Hate to Cook Book. The roll call of artists Knight admires includes Ludwig Bemelmans, Joseph Hirsch, Leo Lionni, Robert Vickrey and Garth Williams.

Over decades, Knight maintained an apartment in midtown Manhattan which also serves as his studio and library, where he adds to his collection of books, sheet music, programs and soundtrack and cast recordings. He is represented by two galleries...the Giraffics Gallery (East Hampton, New York) and Every Picture Tells a Story (Santa Monica, California).