Powell was born and raised in Austin, Texas. She attended Amherst College, graduating in 1995 with a double major in theater and creative writing.

While working for the Lower Manhattan Development Corporation in August 2002, Powell began the Julie/Julia Project, a blog chronicling her attempt to cook all the recipes in Julia Child's Mastering the Art of French Cooking. The blog quickly gained a large following, and Powell signed a book deal with Little, Brown and Company. The resulting book, Julie and Julia: 365 Days, 524 Recipes, 1 Tiny Apartment Kitchen, was published in 2005. The paperback edition was retitled Julie and Julia: My Year of Cooking Dangerously.

Powell's second book, Cleaving: a Story of Marriage, Meat, and Obsession, which details the effects on her marriage of an affair she had after the first book's publication, as well as her experiences learning the butcher trade, was published November 30, 2009.

A film adaptation, also based on Julia Child's autobiography My Life in France, directed by Nora Ephron, and titled Julie & Julia, was released August 7, 2009. It stars Amy Adams as Powell and Meryl Streep as Julia Child.