The Bridesmaids actress will join Leslie Mann and Paul Rudd, who return as troubled couple Pete and Debbie in the tentatively-titled Turning 40.
McCarthy will play a mother whose son attends the same school as the pair's children, according to The Hollywood Reporter.
Her son will apparently be played by Super 8 star Ryan Lee.
Apatow, who is directing the feature, tweeted on July 1: "Four days into the shoot. It feels like the last few days of shooting apocalypse now. I am suicidal in the silver fish. Seems funny though."
Watch Melissa McCarthy in the Bridesmaids trailer below:
The Mike and Molly star is also rumoured to be attached to another Apatow project, which could see her playing opposite Mad Men's Jon Hamm.
McCarthy could be taking on the role of a woman who is pursued romantically by Hamm's character.
Bridesmaids co-star Paul Feig is reportedly planning to direct the film.
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Watch an interview with Melissa McCarthy and Paul Feig below: