Brave was the first Pixar film to feature a female protagonist.
Released in 2012, Brave follows Merida, a Scottish princess who resists an arranged marriage and insists on choosing her own future. She is the daughter of King Fergus and Queen Elinor of DunBroch, and her fierce independence drives the film's conflict.
The story was conceived by Brenda Chapman, who drew inspiration from her relationship with her own daughter. Chapman became Pixar's first female director when she was originally assigned to the project, although Mark Andrews later took over as co-director. Brave was also Pixar's first fairy-tale film and introduced Merida as the first Pixar-created Disney Princess.
Inside Out, Finding Dory, Incredibles 2, and later films also center female protagonists, but they came after Brave. The question refers to Pixar feature films, not every animated film released by Disney or every female character appearing in a Pixar ensemble.