It is located in St. Paul, MN. Although Minneapolis had a long-established orchestra, the Minneapolis Symphony (now the Minnesota Orchestra), its "Twin City," Saint Paul, felt the need for an orchestral organization of its own. The Saint Paul Chamber Orchestra was founded in 1959. Its first concert, on November 18, 1959, was given by its music director, Leonard Sipe.

From the beginning the SPCO stated as it mission to play the classical and contemporary literature "that is not ordinarily played by large symphonies." Over the years, the orchestra has increased its season from four concerts to 150 in a 38-week season. It has won eight ASCAP awards for service in performing new works. It won the Grammy award in 1980 for its recording of the complete score of Aaron Copland's chamber ballet Appalachian Spring.

The SPCO's major conductors have been Dennis Russell Davies (1972-80), Pinchas Zukerman (1980-87), and Hugh Wolff (1992-2000). Under the diverse approaches of these three conductors the orchestra has consistently improved in quality and international acclaim. In 1980 Minnesota Public Radio launched its innovative radio series "St. Paul Sunday Morning," in which host Bill McLaughlin conducts informal conversations with musicians and the orchestra plays. The orchestra also broadcasts its concerts on a network of 100 radio stations, making it the most widely broadcast classical orchestra in the United States.

In 1987 the orchestra instituted an innovative program, appointing a three-member artistic commission (initially comprising Wolff, fellow-conductor Christopher Hogwood and composer John Adams) to advise it on repertory through 1992. In 1990 John Harbison replaced Adams as the composer on the commission.

In addition to Andreas Delfs, appointed in 2001 as music director, the conducting staff comprises principal guest conductor Christopher Hogwood, creative chair conductor Bobby McFerrin, and baroque series director Nicholas McGegan. Aaron Jay Kernis is the composer-in-residence.