He pursued dual careers in academics and music. He was a teaching fellow in general education at Harvard University from 1968 to 1969 and a lecturer in the Department of History of Boston University in 1969. Meanwhile, he began conducting and from 1973 to 1975 he was the principal conductor of the White Mountain Music and Arts Festival.
In 1975, he became President of Bard College in New York and in 1979 president of Simon's Rock College of Bard. Bard College is an innovative liberal arts college in Annandale, New York, founded in 1860, and Simon's Rock is the U.S.'s only liberal arts and sciences college designed for students of high school age, who typically enter it after tenth or eleventh grade and work directly for their bachelors' degrees.
Botstein founded the annual Bard Music Festival, which always focuses on the work of a single composer, invariably presenting newly discovered or new editions of compositions by important composers, which have included Brahms, Mendelssohn, Richard Strauss, Dvorak, Robert Schumann, Bartók, Schoenberg, and Beethoven. The festival includes academic studies and lectures on the composers and their music, and annually publishes with Princeton University Press companion books of essays on the featured composers, as well as bringing highlights of the Festival to Alice Tully Hall at Lincoln Center. Botstein has conducted such major orchestras as the Philharmonia of London, the London Philharmonic, the Royal Scottish National Orchestra, NDR Orchestra of Hannover, and others. In 1992, he was appointed Music Director and Principal conductor of the American Symphony Orchestra, one of the U.S.'s most important orchestras associated primarily with new and American music, and is principal guest conductor of the Hudson Valley Philharmonic and its chamber orchestra. He also directs Bard's The Orchestra Now and is conductor laureate of the Jerusalem Symphony Orchestra.
Botstein is the recipient of many awards, honorary degrees, and fellowships, and is a member of various academic institutes and research groups. He was a visiting faculty member in 1986 of the Manhattan School of Music and professor of the Hochschule für angewandte Kunst in Vienna in 1988. He continues his efforts in musical education with the American Symphony Orchestra by founding several outreach programs. In addition to conducting its regular concerts in the Lincoln Center Great Performers series, he has founded Classics Declassified, an educational series for adult listeners. He has toured with the ASO to Japan and Korea (1994) and in 1998 took it to Brazil to inaugurate a concert hall in São Paulo.
He has published several books and over 100 articles and reviews, and appeared on the Oprah Winfrey Show to discuss his radical proposal to end high schools as they are now known in the United States. He is also editor of The Musical Quarterly.