Maria Semple was born in Santa Monica, California. Her family moved to Spain soon after she was born. There her father, the screenwriter Lorenzo Semple, Jr. wrote the pilot for the television series Batman. The family moved to Los Angeles and then to Aspen, Colorado.
Semple attended boarding school at Choate Rosemary Hall, then received a BA in English from Barnard College in 1986. Her first screenwriting job was in 1992, for the television show Beverly Hills, 90210. She was nominated for a Primetime Emmy, Outstanding Television Series, in 1997 for Mad About You.
In 2006 and 2007, she was nominated for a Writer's Guild of America award, for Arrested Development. This One is Mine was a finalist for the 2010 Pacific Northwest Booksellers Association Award. She appeared in the 2004 David O. Russell film I Heart Huckabees.
She is active in the Seattle literary community, a founding member of Seattle 7 Writers. Her writing has appeared in The New Yorker Magazine. She has also taught fiction writing at the Richard Hugo House.
Semple resides in Seattle Washington.