He was born Oscar Kaplan in Letychiv, Ukraine, son of Jewish parents Mouzya Kaplan and Chana Rapoport. He immigrated to New York at the age of 7.

Among his influential anthologies are Master Poems of the English Language, Immortal Poems of the English Language, The Pocket Book of Modern Verse, and the Little Treasury Poetry Series, which were used in colleges and high schools around the U.S. in the 1950s and 1960s. During his lifetime, anthologies he edited sold more than two million copies, a nearly unheard amount for books of poetry. Many of his anthologies are still being republished today. Though a friend and promoter of poets like Dylan Thomas and George Barker, Williams' own poetry is not highly regarded by critics, though he published several volumes during his life time, and is not nearly as accomplished as the poetry of his wife, the unjustly neglected Gene Derwood (1909—1954).

Among Williams' poems are "Revenge," "Poem," "Poet," "The Last Supper" and "I Sing an Old Song," "The City's Face".

Shopping for Meat in Winter is a typical Williams poem, with its urban theme, forced rhyme, and attempts at replicating the neo-Romanticism of the New Apocalypse.

Shopping for Meat in Winter

What lewd, naked and revolting shape is this?

A frozen oxtail in the butcher's shop

Long and lifeless upon the huge block of wood

On which the ogre's axe begins chop chop.

The sun like incense fumes on the smoky glass,

The street frets with people, the winter wind

Throws knives, prices dangle from shoppers' mouths

While the grim vegetables, on parade, bring to mind

The great countryside bathed in golden sleep,

The trees, the bees, the soft peace everywhere--

I think of the cow's tail, how all summer long

It beat the shapes of harps into the air.

Oscar Williams and his poet-artist wife Gene Derwood sponsored an annual $15,000 poetry award which bears their name.They lived in a penthouse of an office building on Water Street.In his later years, Oscar Williams' home near Wall Street in Manhattan served as a mecca for young poets. Asked how he chose the poems used in his anthologies, he said, "How do you pick one girl to marry? In poetry it's divine polygamy. Generally, when a poem stays with me a long time that poem delivers the goods".

Throughout his life, Oscar Williams eschewed his Jewish background. He was always mysterious about his origins and was buried by an Episcopal Church. He was survived by a son, Strephon Kaplan-Williams, who was raised in boarding schools and hardly ever interacted with his parents. His papers are housed at the Indiana University Lilly Library.