Opera Memphis was chartered in 1956 by a group of Memphians interested in producing regional opera. Charter signatories included noted Memphians Philip Belz and Walter Chandler. Early productions consisted mainly of local singers and local directors. During this initial period the Metropolitan Opera toured regularly through the area and performed in Memphis two to three times per year. As the company grew, the performers and directors became more regional and the sets and costumes more professional. By the mid-1970s, Opera Memphis began bringing in well-known singers like, Leontyne Price, Beverly Sills, Joan Sutherland, Sherrill Milnes, and Birgit Nilsson, to perform in lead roles.

Opera Memphis is widely respected for its education and outreach programs, which currently reach over 14,000 children and adults per season.  From 1993-95, Opera Memphis was the recipient of an Arts Plus Grant from the National Endowment for the Arts. This major funding resulted in student written and produced operas at three Memphis City high schools. Current program offerings include the Artist-in-Residence Tour, Opera 101, Black Roots of Opera, Student Dress Rehearsals and Summer Conservatory.

In March of 2004, Opera Memphis completed a very successful $7.3 million capital drive for the creation and construction of the Clark Opera Memphis Center, a 19,000 square foot administrative center, which includes a rehearsal hall, small performance space, costume shop and small props shop all under one roof in east Memphis. The doors were opened in May of 2003, and Opera Memphis evolved from a small regional opera organization to a world-class opera company seemingly overnight. The Clark Opera Memphis Center has proven to be a popular cultural center for the community, a meeting place for corporate leaders, and a facility that speaks for the arts through both our function and our architecture.

In December of 2010, the Opera Memphis Board of Trust announced Ned Canty as the new Opera Memphis General Director.