[3] Tilson Thomas studied piano with John Crown and composition and conducting under Ingolf Dahl at the University of Southern California, where he graduated from the USC Thornton School of Music '67 and MM '76.

[7] On August 6, 2021, Tilson Thomas disclosed publicly for the first time that he had been diagnosed with an aggressive form of brain cancer, called glioblastoma multiforme.

He proceeded to lead an acclaimed concert of works by Gabriel Fauré, Tilson Thomas' own Meditations on Rilke—wistful reflections on life and death as the composer turned 75 in 2019—and to conclude, a stunning performance of Sergei Prokofiev's monumental Fifth Symphony.

A sampling of Tilson Thomas's own compositions include From the Diary of Anne Frank (1990),[12] Shówa/Shoáh (1995, memorializing the fiftieth anniversary of the bombing of Hiroshima),[13] Poems of Emily Dickinson (2002)[14] and Urban Legend (2002).

Most recently, Tilson Thomas has led two incarnations of the YouTube Symphony Orchestra, which brings young musicians from around the world together for a week of music making and learning.

Tilson Thomas currently serves as president of the Tomashefsky Project, a $2 million undertaking formed in 2017 that is intended to record and preserve his grandparents' theatrical achievements, and is on the faculty of the University of Southern California Thornton School of Music.

That same year, he made his conducting debut with the orchestra, replacing an unwell William Steinberg mid-concert and thereby coming into international recognition at the age of 24.

During a 1985 performance of Mahler's Eighth Symphony at the Hollywood Bowl, a (police) helicopter flew over the venue, disrupting the concert.

"[21] He played an instrumental role in the development of the Frank Gehry-designed New World Center in Miami Beach, which opened in 2011, and currently maintains a relationship with the organization as Artistic Director Laureate.

In April 2005, he conducted the Carnegie Hall premiere of The Thomashefskys: Music and Memories of a Life in the Yiddish Theater, partly as a tribute to his own grandparents.

The Orchestra, as well as such soloists as Mason Bates, Measha Brueggergosman, Joshua Roman, Gil Shaham, Yuja Wang, and Jess Larsen, and participated in a classical music summit in New York City at the Juilliard School over three days.

[31] Tilson Thomas hosted the Keeping Score television series, nine one-hour documentary-style episodes and eight live-concert programs, which began airing nationally on PBS stations in early November 2006.

He and the San Francisco Symphony have examined the lives and music of Gustav Mahler, Dmitri Shostakovich, Charles Ives, Hector Berlioz, Aaron Copland, Igor Stravinsky, Peter Ilyich Tchaikovsky, and Ludwig van Beethoven.

Tilson Thomas has made more than 120 recordings, including works by Bach, Mahler, Beethoven, Prokofiev and Stravinsky as well as his pioneering work with the music of Charles Ives, Carl Ruggles, Steve Reich, John Cage, Ingolf Dahl, Morton Feldman, George Gershwin, John McLaughlin and Elvis Costello.