Lisa Tuttle was born in Houston, TX on September 16, 1952. She was active from an early age in science fiction fandom (she founded and edited the Houston Science Fiction Society's fanzine Mathom while still in high school, and much of her early writing appeared in various fanzines), as well as writing. Tuttle graduated from Syracuse University in 1974 with a BA in English Literature, after which she moved to Austin and became an active member of the Texas science fiction community as well as a journalist for the Austin American-Statesman newspaper.

Tuttle published her first professional short story, "Stranger In The House", in the 1972 Clarion II anthology. In 1973 she helped found the Turkey City Writer's Workshop in Austin, together with Howard Waldrop, Steven Utley, and Tom Reamy. The workshop has graduated a number of important writers, including Bruce Sterling, Ted Chiang, Cory Doctorow, George R.R. Martin, Steven Gould, Maureen McHugh, Lewis Shiner, Martha Wells, and Connie Willis.  In 1974 Tuttle was awarded the John W. Campbell Award for Best New Writer (shared with Spider Robinson).

Tuttle has been writing continuously over the succeeding decades. In 1975 she co-wrote with George R.R. Martin the novella "The Storms of Windhaven", which won the 1976 _Locus_Award for Best Novella and was expanded into the 1981 novel WindhavenTuttle's first). Her other novels include, among others, Lost Futures (1992, nominated for the 1992 BSFA Award for Best Novel, the 1992 James Tiptree Award, and the 1993 Arthur C. Clarke Award for Best Novel), The Pillow Friend(1996, nominated for the 1996 Tiptree Award and the 1996 International Horror Guild Award), The Mysteries (2005), and The Silver Bough(2006). She has written a large number of acclaimed short stories and novellas, including, among others, "Stone Circle" (1976, nominated for the 1977 Nebula Award for Best Novella), "One-Wing" (1980, co-written with Martin and winner of the 1980 _Analog_Award for Best Serial Novel/Novella), "In Translation" (1989, winner of the 1989 BSFA for Best Short Fiction), "And The Poor Get Children" (1995), and "My Death: (2004, nominated for the 2004 International Horror Guild Award for Best Long Form, the 2005 World Fantasy Award for Best Novella, and the 2005 British Fantasy Award for Best Novella).

Tuttle made history in 1982 for being the first, and to date only, writer to refuse a Nebula Award. Her short story "The Bone Flute" was awarded the Nebula for Best Short Story, but Tuttle had already withdrawn it from competition in protest of another nominee having actively campaigned for the award.

She has also written YA fiction, including Catwitch(with illustrator Una Woodruff) (1983), Panther in Argyll(1996) and Love-on-Line (1998). Tuttle has written under different pseudonyms for a number of books. In 1987 she wrote the novel Megan's Story under the name Laura Waring, and Virgo: Snake Inside for a series of twelve young-adult books called Horrorscopes(1995) under the house pseudonym of Maria Palmer. She was a contributing author to Ben M. Baglio's 2000-2002 YA series Dolphin Diaries.

Tuttle has also written non-fiction, including the Encyclopedia of Feminism(1986) and Writing Fantasy and Science Fiction(2002). As editor she has compiled several anthologies, including Skin of the Soul: New Horror Stories by Women(1990), and Crossing the Border: Tales of Erotic Ambiguity(1998) .Her work, both fiction and non-fiction, is known for her focus on strong female characters and on gender issues.

Lisa Tuttle was married from 1981-1987 to fellow SF writer Christopher Priest, and is now married to Colin Murray. The two reside in Scotland. Her recent published works include the "Jesperson and Lane" paranormal mystery series, with The Curious Affair of the Somnambulist and the Psychic Thief (2016) , its 2017 sequel The Curious Affair of the Witch at Wayside Cross, and the latest book in the series, The Curious Affair of the Missing Mummies (2023); and the 2021 Stoker-nominated collection The Dead Hours of Night. Her most recent published collection of stories was Riding The Nightmare, published by Valancourt Books in June 2023.