Patchen was born in Niles, Ohio. His father made his living in the nearby steel mills of Youngstown, Ohio. Those mills would later be referenced in poems like "The Orange Bears" and "May I Ask You A Question, Mr. Youngstown Sheet & Tube?". A major tragedy occurred in Patchen's childhood when his younger sister, Kathleen, was struck and killed by an automobile in 1926. Her death deeply affected him, and he would later pay tribute to her in a poem entitled "In Memory of Kathleen."

He first began to develop his interest in literature and poetry while he was in high school, and the New York Times published his first poem while he was still in college. He attended Alexander Meiklejohn's Experimental College in Madison, Wisconsin for one year, starting in 1929. He then left school and traveled across the country, working itinerant jobs in places like Arkansas, Louisiana, and Georgia.

Next, Patchen moved to the East Coast, living in places like New York City and Boston. While he was in Boston, in 1933, he met Miriam Oikemus at a friend's Christmas party. At the time, Miriam was a college freshman at Massachusetts State College in Amherst. But the two kept in touch, and Patchen started sending her the first of many love poems. They soon fell in love and decided to get married. First Patchen took her to meet his parents in Youngstown, Ohio, then they got married on June 28, 1934 in nearby Sharon, Pennsylvania.

During the 1930s the couple moved frequently between New York City's Greenwich Village and California, as Patchen struggled to make a living as a writer. However, despite his constant struggle, his strong relationship with Miriam supported him and would continue to support him through the hardships that plagued him for most of his adult life.

Indeed, a second major tragedy occurred in Patchen's life in 1937 when he suffered a permanent spinal injury while trying to fix a friend's car. This injury caused him an extreme amount of pain and required multiple surgeries. Although the first two surgeries seemed to help with some of his pain, a botched third surgery ended up leaving him in considerable pain and disabling him for life.

In Patchen's final years, he and his wife moved to a modest house in Palo Alto, California, where Patchen created many of his distinctive painted poems (which he painted while he was confined to his bed). He died in Palo Alto on January 8, 1972.

Throughout his life-time, he was a fervent pacifist (as he made clear in much of his work) and was against U.S. involvement in World War II. This controversial view, coupled with his immobilization, kept him from ever achieving wide recognition or success outside of a cult following.

Patchen's early books of poetry were his most political and caused him to be championed, early on, as a Proletariat Poet. This title, which Patchen rejected, never stuck, since his work varied widely in subject, style, and form. As his career progressed, Patchen continued to push himself into more and more experimental styles and forms, developing, along with writers like Langston Hughes and Kenneth Rexroth, what came to be known as jazz poetry. He also experimented with his child-like "painted poems," many of which are collected in the book What Shall We Do Without Us.

His first book, Before The Brave, was published by Random House in 1936. But after a falling-out with Random House, Patchen signed on with James Laughlin at New Directions Press and started a relationship that would last throughout the remainder of his career. Patchen and Laughlin also became good friends.

During the course of his career, Patchen tried his hand at writing experimental novels such as The Journal of Albion Moonlight and The Memoirs of A Shy Pornographer, as well as the radio play The City Wears A Slouch Hat.

Patchen's Collected Poems was first published in 1968.

One of Patchen's biggest literary supporters was the novelist Henry Miller who wrote a long essay on Patchen, entitled Patchen: Man of Anger and Light in 1946. Patchen also had a close, life-long friendship with the poet E.E. Cummings that began when they were both living in Greenwich Village in the 40's. Later, in the 1950s, Patchen became a major influence on the younger Beat poets like Allen Ginsberg, Lawrence Ferlinghetti, Dick McBride and many other young writers who visited Patchen when they were in California, participating in the West Coast literary scene.

In 1942 Patchen collaborated with the composer John Cage on the radio play The City Wears A Slouch Hat.

In the 1950s, Patchen collaborated with Charles Mingus, reading his poetry with Mingus' jazz combo. No known recording of their collaboration exists.

Moe Asch of Folkways Records made some recordings of Patchen reading his poetry and excerpts from one of his novels. These recordings were released as Kenneth Patchen Reads with Jazz in Canada (1959), Selected Poems of Kenneth Patchen (1960), and Kenneth Patchen Reads His Love Poems (released 1961). From Albion Moonlight was recorded later at Patchen's home but not released until 1972 by Folkways.

The Jazz in Canada album was recorded in Vancouver and was recorded the same week as a live performance done for CBC Radio. The LP was also released on Folkways and included a mimeographed pamphlet featuring poems and the jazz musicians credits. The group playing on the recording was the Allan Neil Quartet. It was released on CD by the label Locust Music in 2004.

On January 21, 2008, El Records released a recording entitled Rebel Poets in America that includes classic poetry readings with jazz accompaniment by both Kenneth Patchen and Lawrence Ferlinghetti, including Patchen classics like "The Murder of Two Men by a Young Kid Wearing Lemon Colored Gloves" and "I Went To The City." These Patchen recordings were made in collaboration with the musician Allyn Ferguson who composed and arranged jazz accompaniment for each individual poem and also led the jazz ensemble.