Sanders was born in Kansas City, Missouri. He dropped out of the University of Missouri in 1958 and hitchhiked to New York City’s Greenwich Village to attend New York University. He wrote his first major poem, Poem from Jail, on toilet paper in his cell after being jailed for protesting against the launching of nuclear submarines armed with nuclear missiles in 1961.

In 1962, he founded the avant-garde journal, Fuck You . Sanders opened the Peace Eye Bookstore (at 383 East Tenth Street in what was then the Lower East Side), which became a gathering place for bohemians, writers and radicals.

Sanders graduated from New York University in 1964, with a degree in Greek. In late 1964 he founded The Fugs with Tuli Kupferberg. The band broke up in 1969 and reformed in 1984.

On October 21, 1967, he helped The Fugs, the San Francisco Diggers and others in his attempt to exorcise the Pentagon.

In 1971, Sanders wrote The Family, a profile of the events leading up to the Tate-LaBianca murders. He attended the Manson group's murder trial, and spent time at their lair at the Spahn Movie Ranch. There have been two updated editions of The Family, the most recent in 2002. ."

Sanders is the founder of the Investigative Poetry movement. His 1976 manifesto, Investigative Poetry, published by Lawrence Ferlinghetti’s City Lights Books, had an impact on investigative writing and poetry during the ensuing decades.

In the 1990s Sanders began utilizing the principles of Investigative Poetry to create a series of book-length poems on literary figures and American History. Among the fruits of this work, are Chekhov, a biography in verse of the great playwright and short story writer; 1968, a History in Verse; The Poetry and Life of Allen Ginsberg, and America, a History in Verse.

In 1998, Sanders began work on a 9-volume America, a History in Verse. The first five volumes, tracing the history of the 20th century, have been completed and published in a fully indexed CD format, over 2,000 pages in length.

Sanders received Guggenheim Fellowship in poetry in 1983, and a National Endowment for the Arts Fellowship in poetry for 1987. His Thirsting for Peace in a Raging Century, Selected Poems 1961-1985, won an American Book Award in 1988. He was chosen to deliver the Charles Olson Memorial Lectures at SUNY Buffalo in 1983. In 1997 Sanders received a Writers Community residency sponsored by the YMCA National Writer’s Voice through the Lila Wallace Readers Digest Fund.

In 2000 and 2003 Sanders was Writer-in-Residence at the New York State Writers Institute in Albany, NY.

In 1997 he was awarded a grant from the Foundation for Contemporary Arts Grants to Artists Award.

As of 2009, Sanders lives in Woodstock, New York where he publishes the online Woodstock Journal with his wife of over 47 years, the writer and painter Miriam R. Sanders. He also invents musical instruments including the Talking Tie, the microtonal Microlyre and the Lisa Lyre, a musical contraption involving light-activated switches and a reproduction of Da Vinci's Mona Lisa.