At age 16 Chávez completed Sinfonía, his first symphony. The ballet El fuego nuevo (1921; “The New Fire”) was his first significant work in a Mexican style. He traveled in Europe and the United States, and in 1928 he founded and became conductor of the Symphony Orchestra of Mexico. From 1928 to early 1933 (and again for part of 1934) he was director of the national conservatory in Mexico.

Chávez's music is unmistakably Mexican in its melodic patterns and rhythmic inflections. From indigenous Mexican music he took the uses of percussion, straightforward rhythms, and old forms of harmony and melody. He was also influenced by modern European and American composers, especially Igor Stravinsky (Stravinsky, Igor) and Arnold Schoenberg (Schoenberg, Arnold).

Among his best-known compositions are two early symphonies, Sinfonía de Antígona (1933) and Sinfonía India (1935), both one-movement works using indigenous themes. The Concerto No. 1 for piano and orchestra (1940) is highly percussive. The Toccata for percussion instruments (1942) is scored for 11 types of percussion instruments, some of them indigenous, played by six performers. Chávez's other works include the ballet Los cuatro soles (1925; “The Four Suns”), Xochipilli Macuilxochitl for orchestra with indigenous instruments (1940), the Violin Concerto (1949–50), Discovery for orchestra (1969), and the Trombone Concerto (1975–76). Chávez published numerous essays on Mexican music and Toward a New Music (1937); his Charles Eliot Norton lectures (1958–59) at Harvard University were collected in Musical Thought (1961).