Kerouac was born in Albany, New York. Her mother left her father while pregnant, and Jack refused to acknowledge the baby as his daughter. A blood test when Jan was nine years old proved his paternity and he was ordered to pay $52 a week for her upbringing. Though Jan met her father only twice, she inherited his wanderlust, and like both her parents, Jan made frequent use of drugs and was no stranger to trouble. After a teenage stint in a mental hospital, Jan delved deeper into the 1960s underworld of drugs, before leaving for Mexico at the age of fifteen. For the next few decades, she traveled across the country with a reckless abandon that echoed that of her father and Neal Cassady.

She published two semi-autobiographical novels, Baby Driver in 1981, and Trainsong in 1988. She was working on a third novel, Parrot Fever, at the time of her death.

During this time, Kerouac was also involved in legal battles with Stella Sampas Kerouac, Jack's last wife; and after Stella's death, with Stella's blood relatives, over his estate, including the location of his grave and ownership of his papers. On July 24, 2009, a judge in Pinellas County, Florida ruled that the will of his mother Gabrielle Kerouac (died 1973), which gave all rights to Jack Kerouac's work to the Sampas family, was a forgery. The legal action against this will was originally brought by Jan Kerouac and a nephew of Jack's.

It is not clear whether the judge's ruling would affect the distribution of assets of the estate. A lawyer for the Sampas family, George Tobias, commented that he expected the ruling to be appealed. He did not explain how this would occur, since the family was not directly involved in the lawsuit.

Married and divorced twice, Kerouac lived a troubled life marked by periods of self-destruction. In 1968, she gave birth to a stillborn child and had no other children.

On June 5, 1996, Kerouac died in Albuquerque, New Mexico following surgery. She is survived by twin half-sisters, Katharine and Sharon, and one half-brother, David Bowers.

Author Gerald Nicosia, who at one time was Jan Kerouac's personal literary representative, has edited and published a book of tributes to her, entitled Jan Kerouac: A Life in Memory in January 2009.