Karla Kuskin was the only child of Sidney and Mitzi Seidman and was raised in Greenwich Village, New York City. She went to Little Red School House, followed by Elizabeth Irwin High School. She then attended Antioch College in 1950—53, and transferred to Yale where she studied with, among others, Josef Albers, Herbert Matter and Alvin Eisenman. Kuskin earned her B.F.A in graphic design in 1955 from Yale. Her first book, “Roar and More” (Harper, 1956), was born of her senior graphic-arts project at Yale, for which she had to design and print a book on a small press. She was married to Charles M. Kuskin, oboist, from 1955—1979 and in 1989 married William L. Bell Jr, counsel for the Center for Naval Analyses. She had two married children from her first marriage, three married stepchildren and five grandchildren. She lived and worked in Brooklyn for most of her life, moving to Bainbridge Island, Washington, then settling in Seattle at the end of her life. Before working a full-time author, Kuskin worked as an assistant to a fashion photographer, a design assistant, and in advertising.

In August 2009, Kuskin died of corticobasal degeneration in Seattle, aged 77.

Kuskin wrote or illustrated more than 65 books, and of those, she wrote and illustrated nearly half. She collaborated with well-known authors and illustrators, illustrating a book authored by Paula Fox and writing two books illustrated by Marc Simont. She also incorporated a series of illustrations by Milton Avery, originally for a never-completed children's book project, nearly thirty years after the painter's death.

She occasionally used the pen-name "Nicholas J. Charles".

Kuskin, a prolific writer not only of but also about children's literature, wrote often for The New York Times Book Review.

Roar and More (1956)James and the Rain (1957)In the Middle of the Trees (poems) (1958)The Animals and the Ark (1958)Just like Everyone Else (1959)Which Horse Is William? (1959)Square as a House (1960)The Bear Who Saw the Spring (1961)All Sizes of Noises (1962)Alexander Soames: His Poems (1962 - Under pseudonym Nicholas J. Charles)How Do You Get from Here to There? (1962)ABCDEFGHIJKLMNOPQRSTUVWXYZ (1963)The Rose on My Cake (poems) (1964)Sand and Snow (1965 - Under pseudonym Nicholas J. Charles)Jane Anne June Spoon and Her Very Adventurous Search for the Moon (1966)The Walk the Mouse Girls Took (1967)Watson, the Smartest Dog in the U.S.A. (1968)In the Flaky Frosty Morning (1969)Any Me I Want to Be (poems) (1972)What Did You Bring Me? (1973)Near the Window Tree (poems and notes) (1975)A Boy Had a Mother Who Bought Him a Hat (1976)Herbert Hated Being Small (1979)Dogs and Dragons, Trees and Dreams (A Collection of Poems) (1980)Night Again (1981)Something Sleeping in the Hall (1985)Soap Soup (1992)City Dog (1994)

A Space Story, illustrated by Marc Simont (1978)The Philharmonic Gets Dressed, illustrated by Simont (1982)The Dallas Titans Get Ready for Bed, illustrated by Simont (1986)Jerusalem, Shining Still, illustrated by David Frampton (1987)A Great Miracle Happened There: A Chanukah Story, illustrated by Robert Andrew Parker (1993)Paul, paintings by Milton Avery (1994)Patchwork Island, illustrated by Petra Mathers (1994)City Noise, illustrated by Renee Flower (1994)James and the Rain, illustrated by Reg Cartwright (1995)The Upstairs Cat, llustrated by Howard Fine (1997)The Animals and the Ark, illustrated by Michael Grejniec (2002)The Sky Is Always in the Sky, illustrated by Isabelle Dervaux (1998)I Am Me, illustrated by Dyanna Wolcott (2000)Moon, Have You Met My Mother? The Collected Poems of Karla Kuskin, illustrated by Sergio Ruzzier (2003)Under My Hood I Have a Hat, illustrated by Fumi Kosaka (2004)Ice Cream Dreams, illustrated by Lewis Matheney (2005)Toots the Cat, illustrated by Lisze Bechtold (2005)So What Is It Like to Be a Cat?, illustrated by Betsy Lewis (2005)

Traces written by Paula Fox, illustrated by Karla Kuskin 2008.

Thoughts, Pictures, and Words, photographs by Nicholas Kuskin (1995)