The company, originally named Cincinnati Opera Association, gave its first performance, Flotow's Martha, on 27 June 1920. During its early days, members of the Association also raised funds to mount the world premiere of Ralph Lyford's opera Castle Agrazant which took place at the Cincinnati Music Hall on 29 April 1926.
For most of its first fifty years, Cincinnati Opera's performances were held at the Cincinnati Zoo Pavilion. During that time, many prominent singers appeared in the company's productions including Plácido Domingo, Beverly Sills, Norman Treigle, Sherrill Milnes, Montserrat Caballé, Jan Peerce, Robert Merrill, Roberta Peters, Shirley Verrett, Lawrence Tibbett, Richard Tucker, Martina Arroyo, James Morris, Elinor Ross and Barbara Daniels. In 1972, Cincinnati Opera moved its performance base to the newly renovated Cincinnati Music Hall.
James de Blasis became the company's Resident Stage Director in 1968. He then served as its General Director from 1973 to 1987. In 1988 he became its Artistic Director, a post which he held until 1996.
Under his tenure, the company began to program rare operas such as Maxwell Davies' Resurrection and Weinberger's Schwanda the Bagpiper. It also added musicals to its repertory in an effort to broaden its audience base. One of the highlights of the de Blasis era was a new interpretation of Donizetti's L'elisir d'amore which changed the setting from the Basque region of Spain in the 1820s to the "Wild West" of late 19th century Texas. The production was filmed by PBS and nationally televised in 1968.
In 1996, the internationally known stage director, Nicholas Muni, succeeded James de Blasis as Artistic Director of the company. Under his leadership Cincinnati Opera further enlarged its repertory with many company premieres outside the standard reportory including Janáček's Jenůfa, Britten's The Turn of the Screw, Debussy's Pelléas et Mélisande, Bartók's Bluebeard's Castle, Schoenberg's Erwartung, Heggie's Dead Man Walking, Strauss' Elektra, Poulenc's La Voix Humaine, Weill's The Seven Deadly Sins, Ullmann's The Emperor of Atlantis, and the U.S. premiere of Peter Bengtson's The Maids. The company also performed its first mainstage commission, Richard Danielpour's Margaret Garner (co-commissioned with Michigan Opera Theatre and Opera Company of Philadelphia). The Cincinnati performances coincided with the opening of Cincinnati's National Underground Railroad Freedom Center and starred Denyce Graves in the title role.
In 2006, Evans Mirageas, an influential casting director and former head of Decca's Artists & Repertoire division, became Cincinnati Opera's new Artistic Director. Following his first season with the company, Opera News magazine listed him as one of the "25 Most Powerful Names in U.S. Opera".
The 2008 Summer Festival, the first to be fully programmed by Mirageas, included the French version of Donizetti's Lucia di Lammermoor plus the company premiere of Daniel Catán's Florencia en el Amazonas. The company's 2009 season, under the title of "Opera Goes to Spain", presented the regional premiere of Osvaldo Golijov's Ainadamar. The 2010 season presented a 90th Anniversary Gala Concert (featuring, among others, guest host Ryan Seacrest and soprano Angela Brown). Following in 2011 was John Adams' A Flowering Tree, while the 2012 season presented the rare Piazzolla's María de Buenos Aires.
Beginning in 2013, Cincinnati Opera is planning on expanding its seasons to be true "festivals" featuring grand opera performances in Music Hall; lectures, films and recitals in Memorial Hall; outdoor concerts in Washington Park; and small-scale opera productions at CCM. Performances outside of the standard repertory which have been scheduled for 2013 include Glass' Galileo Galilei.
Performances scheduled for 2014 include Francesco Cavalli's La Calisto and Kevin Puts's Silent Night, recipient of the 2012 Pulitzer Prize for Music. In 2015, operas outside the standard repertoire include the world premiere of Ricky Ian Gordon and William M. Hoffman's Morning Star.