The pair are raising money for Anamolisa on crowd-funding platform Kickstarter, aiming for a goal of $200,000 (£129,000) to fund the film.
Dino Stamatopolous, who created dark stop-motion series Moral Orel and appeared on Community as Starburns, is also executive producing.
The film is about a motivational speaker whose own life has become hollow and meaningless, before meeting a girl who inspires him to escape on an adventure.
"We've been working in the television and movie industry for years and we just want to make something ourselves. Something pure. Something beautiful," they added.
Both Kaufman and Harmon have battled against the influence of studios and executives on their work - Kaufman has said that he is "not interested in trying to please people", while Harmon's dogged insistence on creative control is rumoured to have cost him his job on Community.
Watch the Kickstarter video for Anamolisa below: