Its first director was Albert Stoessel, the young man who had conducted the New York Symphony in most of its Chautauqua appearances. With the opening of Norton Memorial Hall, a monolithic concrete structure, Chautauqua now had the facilities for opera and dramatic presentations as well as concerts and recitals. The Chautauqua Symphony Orchestra could now provide a pit orchestra for the new Chautauqua Opera Association. Stoessel made use of former New York State members, some of whom now played with the Philharmonic; most still played with Walter Damrosch for a nationally broadcast Music Appreciation Series as well. Until his death in 1943, Stoessel directed the life of the orchestra, the opera and the School of Music. Under the directorship, despite the effects of the depression on the newly formed group, the Chautauqua Orchestra grew in stature, with children's concerts, chamber music affiliates, and national radio broadcasts (21 in 1932) to its credit. In keeping with Chautauqua's educational and cultural mission, Stoessel's aim was to present the best of modern music, including American works, as well as a liberal amount of the classic repertoire. This pattern has continued.

Another program innovation of the Stoessel years deserves mention, the use of The Little Symphony, conducted by the Orchestra's associate conductor, Georges Barrere. Consisting usually of 25 musicians from the larger orchestra, this group most often provided the concerts the first week of the orchestra season, and was greatly appreciated.

Upon Stoessel's death Franco Autori became the second regular conductor of the Chautauqua Symphony Orchestra. In nearby Buffalo, Autori had transformed a Federal Music Project into a community-supported orchestra, and at Chautauqua, he continued Stoessel's policy of programming American works along with the standard repertoire. Autori was followed in 1953 by Walter Hendl, music director of the Dallas Symphony. Knowledgeable, painstaking, imaginative and alert to modern trends, Hendl continued to program monumental works of the symphonic repertoire and contemporary music. He remained with Chautauqua until temporary ill health necessitated his resignation in 1972.(In Chautauqua's early years the Juilliard School of Music had exerted considerable influence. Later a significant influence was felt from the Eastman School of Music in Rochester.)

Following several years of guest conductors and the brief tenure of Baltimore Symphony Music Director Sergiu Comissiona, Varujan Kojian was selected in late 1980 to become Chautauqua's fifth music director.

A rising young conductor with an international reputation, Kojian was then music director of the Utah Symphony. He had also served as conductor of the Stockholm Radio Orchestra and principal guest conductor of the Royal Swedish Opera. He remained at Chautauqua for four years.

The orchestra's concertmaster, Millard Taylor, was engaged to assist with programming for the CSO during 1985 and 1986 before the appointment of Joseph Silverstein as music director and principal conductor in the fall of 1986. A widely recognized musician of international acclaim, he was a strong leader and program builder for the orchestra. His appearances as violin soloist are eagerly anticipated during the summer by Chautauquans who also enjoy his pre-concert lectures. From 1990 to 2007, Israeli conductor, Uriel Segal, was the seventh music director. Under his guidance, the orchestra was increased from 74 to 76 musicians. He was instrumental in putting into place a more rigorous audition process that resulted in a very high caliber of new orchestra members. His leadership has seen a tremendous increase in musical quality, while continuing the tradition of a commitment to diverse repertoire. Segal's tenure is also recognized for his identification and support of burgeoning artists, introducing them as soloists to Chautauqua audiences.

From 2007-2010, German-born conductor Stefan Sanderling was appointed as the eighth music director of the Chautauqua Symphony Orchestra.

From 2011 to the present, the CSO has continued to present outstanding concerts. Vice President Marty Merkley, with the help of several CSO musicians, has engaged notable guest conductors and soloists from around the world and chosen excellent repertoire.

The orchestra makes its home in the Amphitheater, Chautauqua's program center. With its 1893 all-wood construction, good acoustics for music are assured. Wooden benches provide seating for approximately 4,000, while its three open sides give a sense of informality and spaciousness.