Kelly Fremon Craig is writing and directing the film with James L. Brooks producing through Gracie Films. The duo previously collaborated on Craig's The Edge of Seventeen.
Production will begin in April. Blume is also producing alongside Julie Ansell, Richard Sakai and Amy Brooks.
Are You There God? It's Me, Margaret was published in 1970 and follows Margaret, a sixth grader going through puberty who is looking for answers.
"My readers are always fantasy-casting my books, but I've never done that. But you know it when you see it, and Abby is a natural. And I'm so excited that Margaret got a funny, sexy, sassy mom in Rachel," Blume said while speaking with Entertainment Weekly.