Born to Chinese parents, Ma was a child prodigy and at age five gave his first public recital. He later moved to New York City with his family and made his Carnegie Hall debut at age nine. He studied at the Juilliard School under Leonard Rose and János Scholz before graduating from Harvard University (1977) with a degree in humanities. He was the recipient of the Avery Fisher Prize in 1978, and in 1991 Harvard awarded him an honorary doctorate in music.

Ma became celebrated for performances and recordings of the standard cello repertoire and for receiving an unusually large number of commissions from contemporary composers. He frequently performed as part of a trio with pianist Emanuel Ax and violinist Young-Uck Kim and as part of a quartet with Ax, Stern, and violinist Jaime Laredo. Ma and Ax received high acclaim for their recordings of the sonatas of Ludwig van Beethoven (Beethoven, Ludwig van) (1985) and Johannes Brahms (Brahms, Johannes) (1991). Of special interest to Ma were the six suites for unaccompanied cello by Johann Sebastian Bach (Bach, Johann Sebastian), challenging masterpieces that were some of the first music he learned to play as a young boy. He recorded the suites in 1983 and again in 1998. Accompanying the latter release was a series of six films that interpreted Bach's suites; Ma collaborated on the project with artists from such varied disciplines as choreography, landscape architecture, ice skating, film directing, and Kabuki theatre.

In addition to his conventional repertoire, Ma also recorded with improvisational singer Bobby McFerrin on Hush (1992) and with bluegrass musicians on Appalachia Waltz (1996) and Appalachian Journey (2000). On Soul of the Tango (1997), he recorded the tangos of Astor Piazzolla (Piazzolla, Astor). He also played on Crouching Tiger, Hidden Dragon (2000), the soundtrack recording for the movie of the same name, and in 2003 collaborated with Latin American musicians on Obrigado Brazil. In 1998 Ma founded the Silk Road Project, an arts organization that explored the cultural traditions along the Silk Road, an ancient trading route that linked China with the West. Soon after he established the Silk Road Ensemble, and the group's first recording, Silk Road Journeys: When Strangers Meet, was released in 2002; further Silk Road recordings were released in 2002, 2005, 2007, and 2008. A prolific musician, Ma recorded more than 50 albums between 1983 and 2008, and during this time he received 15 Grammy Awards.