Washington was born in 1981 and raised in Los Angeles, California. He is a graduate of the Academy of Music of Alexander Hamilton High School in Beverlywood, Los Angeles. Washington next enrolled in UCLA's Department of Ethnomusicology, where he began playing with faculty members such as Kenny Burrell, Gerald Wilson, and Billy Higgins, who mentored a quartet with Washington, pianist Cameron Graves, and the brothers Stephen ("Thundercat") and Ronald Bruner. They released their debut album Young Jazz Giants in 2004 on Birdman Records.
Washington joined the Gerald Wilson Orchestra for its 2005 album In My Time. In 2008 and 2009 "The Kamasi Washington Band" played the outdoor Labor Day Jazz Concert on the Main Green at Village Green, Los Angeles. Washington played saxophone on Kendrick Lamar's album To Pimp a Butterfly, released on March 25, 2015. Washington's debut solo recording, The Epic, was released in May 2015. Washington contributed saxophone on the Thundercat song "Them Changes", which was released on June 18, 2015, as a single from the EP The Beyond / Where the Giants Roam; the track was later included on Thundercat's full-length album Drunk (2017).
Washington released the mini-album/EP Harmony of Difference in September 2017. This was followed by his second full-length studio album, Heaven and Earth, which was released in June 2018, with a companion EP titled The Choice released a week later.
Washington at Coachella Valley Music and Arts Festival in 2016
Washington has played along with a diverse group of musicians including Wayne Shorter, Herbie Hancock, Horace Tapscott, Lauryn Hill, Nas, Snoop Dogg, George Duke, Chaka Khan, Flying Lotus, Mike Muir, Francisco Aguabella, St. Vincent, the Pan Afrikaan People's Orchestra, Run the Jewels and Raphael Saadiq.
On June 25, 2020, Washington, Terrace Martin, Robert Glasper, and 9th Wonder announced the formation of the supergroup Dinner Party. They released a single, "Freeze Tag", and their debut extended play, Dinner Party, was released on July 10, 2020.
On June 18, 2021, Washington released a new song "Sun Kissed Child" as part of The Undefeated's Music for the Movement series. Also in 2021, Washington and his band contributed a cover of the Metallica song "My Friend of Misery" to the charity tribute album The Metallica Blacklist.