Lathan, who earned a Tony nomination for "A Raisin in the Sun," which also starred Sean "Diddy" Combs, will play the title character, a headstrong African-American maid and budding actress.
Nottage, who won a Pulitzer Prize for her play "Ruined," draws on the screwball films of the 1930s to take an irreverent look at racial stereotypes in Hollywood.
The production will begin previews April 6 and open May 9 off-Broadway at Second Stage Theatre.
Lathan recently starred in the London revival of "Cat on a Hot Tin Roof." She played Isabella in "Measure for Measure" opposite Billy Crudup at The Public Theater's Shakespeare in the Park.