Lisa was born in Kingsport, Tennessee, where she went to public schools. She was graduated from Wellesley College with a BA in English literature in 1966.

She had a priviledged upbringing and went to Wellesley College during the 1960s where she experienced the events fictionalized in her famous novel, Kinflicks (1976).

As in others of Alther's novels, lesbianism is portrayed as one of several possibe versions of how one might live one's life. Alther's heroines tend not to have a single sexual identity but move from lesbian relationships to heteresexual ones, or vice versa.

She taught Southern Fiction at St. Michael's College in Winooski, Vermont. Having lived in London and Paris, she currently divides her time between Vermont and New York City.