The orchestra was founded as the City of Birmingham Orchestra in 1920, with Edward Elgar conducting its first concert in September of that year. The programme included Overture: Saul by Granville Bantock, a strong supporter of the orchestra's foundation. Adrian Boult was chief conductor from 1924 to 1930.

The CBO became a full time organisation in 1944, changing its name to the City of Birmingham Symphony Orchestra in 1948. The composer Andrzej Panufnik was chief conductor from 1957 to 1959.

The orchestra made recordings and gave regular concerts, but gained international renown only after Simon Rattle became its chief conductor in 1980. Under him, the orchestra became one of the leading ensembles in Europe, and gained a name for its interpretations of late romantic and 20th century works, especially those of Sibelius and Gustav Mahler. During this period, the orchestra moved from Birmingham Town Hall to a new "home venue", Symphony Hall, inside Birmingham's International Convention Centre. The nearby CBSO Centre, a converted factory, houses management offices, rehearsal facilities, and is a concert venue in its own right, for more intimate performances. In 1990, the post of Radcliffe Composer in Association was created, with Mark-Anthony Turnage filling the role. In 1995 Judith Weir became Fairbairn Composer in Association, followed in 2001 by Julian Anderson.

The Finn Sakari Oramo took over from Sir Simon Rattle in 1998, Rattle subsequently securing the post of Music Director of the Berlin Philharmonic. Oramo has announced that he will step down in 2008 and take the title of principal guest conductor.

In 2001, the players rejected of a contract that would have stopped extra payments for broadcasts and recordings, in the context of financial crisis at the CBSO. In addition, other controversy arose from the CBSO's demands from the Arts Council for a greater share of the Council's stabilisation fund, because of its reputation compared to other British orchestras.

The CBSO has recorded substantially for EMI Classics and Warner Classics, as well as smaller labels.

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