The Independent Spirit Award for Best Female Lead was one of the annual Independent Spirit Awards to honor an actress who has delivered an outstanding lead performance in an independent film. It was first presented in 1985 with Geraldine Page being the first recipient of the award for her role as Carrie Watts in The Trip to Bountiful. It was last presented in 2022 with Taylour Paige being the final recipient of the award for her role in Zola.

In 2022, it was announced that the four acting categories would be retired and replaced with two gender neutral categories, with both Best Male Lead and Best Female Lead merging into the Best Lead Performance category.

With two wins, Frances McDormand and Julianne Moore are the most awarded females in this category, while with 4 nominations Michelle Williams is the most nominated female in this category.