Mule Bone was produced for the first time in 1991 by the Lincoln Center Theater, more than 60 years after it was written. It opened at the Ethel Barrymore Theatre on Broadway on February 14, 1991, to generally negative reviews.
Reviewing Mule Bone for The New York Times, Frank Rich wrote that it was "an evening that can most kindly be described as innocuous". He described it as a "broad, often bland quasi-musical". Also writing in The New York Times, David Richards said of Mule Bone: "it's just not a very good play." Both critics suggested the play might have been much better had Hughes and Hurston finished their collaboration.
The production closed on April 14, 1991, after 68 performances.