Angela Bassett and Jennifer Hudson are also in negotiations to star in the gospel musical, reports Variety.
Director Kasi Lemmons has been working on the adaptation of Langston Hughes's 1961 Broadway production, which centres around a black teenager from Baltimore who is sent by his mother to stay with his grandparents in Harlem, having never met them before.
The boy experiences stylised dream sequences recounting the nativity story and learns the true meaning on family and faith.
Jackson will play the grandfather, Reverend Clarence Cobbs, with Bassett as his wife Aretha.
The Pulp Fiction star was last seen in Avengers and is in line to appear in Captain America 2, the RoboCop remake and Quentin Tarantino's Django Unchained.
Bassett will appear in the forthcoming Olympus Has Fallen.