He married Mary Ellen (Nellie) Meriwether Henderson (1886-1976), also a teacher and civil rights advocate, as well as active with the Girl Scouts and League of Women Voters. They moved to Falls Church, Virginia in 1910 shortly after their marriage, and both helped at the Henderson family store. They lived at 307 South Maple Street (originally 307 W. Fairfax Street) for decades; Edwin Henderson also took the colored streetcar line across the Potomac River to his job with the D.C. Public Schools. They also had a summer home at Highland Beach on Chesapeake Bay near Annapolis, Maryland. The Hendersons remained married for 63 years until her death (almost a year before his demise), and were survived by both their sons: Dr. James H. M. Henderson (who became director of Tuskegee's Carver Research Foundation), Dr. Edwin M. Henderson (who became a dentist in the District of Columbia).