Marin's trademark is his characters' strong Mexican accents; this is part of his comic persona, as he was born and raised in the United States.

Marin was born in Los Angeles, California, the son of Oscar Marin, a policeman in the LAPD, and his wife Elsa (Meza), a secretary. He is Mexican American. Marin was born with a cleft lip, which was repaired. He speaks some Spanish and uses it in his movies, but he is not fluent.

Marin's nickname "Cheech" is short for "chicharron", a fried pork skin that is a popular snack in Mexican cuisine and a favorite of marijuana smokers afflicted with "the munchies", and the nickname's alliteration with Chong's surname made "Cheech and Chong" an obvious choice for the name of the duo.

Marin graduated from Bishop Alemany High School, and then studied at San Fernando Valley State College (now California State University, Northridge), where he was a member of Phi Sigma Kappa. He dropped out before graduating. Marin auditioned to sing for Frank Zappa in 1967, but he moved to Vancouver, British Columbia in September to dodge the draft during the Vietnam War. Marin met his future comedic partner, Tommy Chong, in Calgary, Canada.

As a part of the highly successful comedy duo Cheech & Chong, Marin participated in a number of comedy albums and feature film comedies in the 1970s and 1980s. Tommy Chong directed four of their films, while co-writing and starring in all seven with Marin.

After Cheech & Chong disbanded in 1985, Marin starred in a number of films as a solo actor, most notably Born in East L.A., The Shrimp on the Barbie, Tin Cup, and Once Upon a Time in Mexico. He made a cameo appearance as a dockworker in Ghostbusters II.

Marin made the transition to full-time television work when he co-starred on the short-lived The Golden Girls spin-off The Golden Palace (1992–1993), and later with Don Johnson, Jaime P. Gomez and Yasmine Bleeth in the police show Nash Bridges (1996–2001), in which they played San Francisco police-detective partners. In recent years he has been active in playing supporting roles in films and performing voice overs for animated features. After appearing in a supporting role in Judging Amy, playing an independently wealthy landscape designer, Marin starred in the CBS sitcom Rob, with Rob Schneider.

Marin is a frequent collaborator of the director Robert Rodriguez, who has worked with Marin seven times; the last two installments of the Mexico trilogy, the Spy Kids trilogy, From Dusk Till Dawn and Machete. He provided his voice for several Disney animated films, most notably Tito in Oliver & Company (1988), Banzai in The Lion King (1994) and Ramone in Cars (2006) and its sequel Cars 2 (2011). He reprised the Banzai role in the video game Kingdom Hearts II.

Marin has released two best-selling albums in the children's music genre, My Name is Cheech, the School Bus Driver (1992) and My Name is Cheech, The School Bus Driver "Coast to Coast" (1997). Both albums were released bilingually. In July 2007, the book Cheech the School Bus Driver was released, written by Marin, illustrated by Orlando L. Ramirez, and published by HarperCollins.

In 2005, Marin lent his voice to the animated children's series Dora the Explorer. He appeared in the episode "A Crown for King Bobo", as the Puerto Rican folk hero Juan Bobo.

In late 2006, Marin participated in Simon Cowell's Celebrity Duets, having sung with Peter Frampton, Randy Travis, Clint Black, Aaron Neville, and Al Jarreau. He was the fourth to be eliminated. In that same year, he voiced as Gaspar Gomez in Scarface: The World Is Yours.

In recent years, Marin has had a recurring role in the hit television series Lost, playing David Reyes, Hurley's father.

He was a co-host for WWE Raw on March 1, 2010 with his comedy partner Tommy Chong, in Oklahoma City.

Marin also sings on the hidden track "Earache My Eye" on Korn's album Follow the Leader.

On March 18, 2010, Marin beat journalist Anderson Cooper and actress Aisha Tyler on Celebrity Jeopardy!'s Million Dollar Celebrity Invitational. Cooper admitted he was "crushed" by Marin. Marin also won his semifinal round early May but lost in the May 6–7 final to Michael McKean. He had previously won the first Celebrity Jeopardy! tournament in 1992.

In January 2012, he was one of eight celebrities participating in the Food Network reality series Rachael vs. Guy: Celebrity Cook-Off. He was eliminated on the third week of the competition.^]

Marin is an avid collector of Chicano art. Two national touring exhibitions have featured works from his private collection. Marin started collecting Chicano art in the 1980s. He feels that it's important to "use his celebrity status to call attention to what he saw as an under-appreciated and under-represented style of art."

He is also an avid golfer, although he initially disliked the sport until he co-starred in Tin Cup.

Marin was married in 1975 to Darlene Morley, who co-produced Cheech & Chong's The Corsican Brothers and also played minor roles in earlier Cheech & Chong films under the name Rikki Marin. The couple had one child and divorced in 1984. Marin married artist Patti Heid in 1986; they had two children and have since divorced. Patti is responsible for his interest in Chicano Art. Marin married his longtime girlfriend, Russian pianist Natasha Rubin, on August 8, 2009, in a sunset ceremony at their home.

As a youth, Tommy Chong moved with his family to Calgary, settling in a conservative neighbourhood Chong has referred to as "Dog Patch". He has said that his father had "been wounded in World War II, and there was a veterans hospital in Calgary. He bought a $500 house in Dog Patch and raised his family on $50 a week."

By the early 1960s, Chong was playing guitar for a Calgary soul group called The Shades. The Shades moved to Vancouver, British Columbia, where the band's name changed to "Little Daddy & The Bachelors". They recorded a single, "Too Much Monkey Business" / "Junior's Jerk". Together with bandmember Bobby Taylor, Chong opened a Vancouver nightclub in 1963. Formerly the Alma Theatre, they called it "Blue Balls". They brought in the Ike & Tina Turner Revue, which had never been to Vancouver before. Although Little Daddy & The Bachelors built up a small following, things soured when they went with Chong's suggestion and had themselves billed as "Four Niggers and a Chink" (or, bowing to pressure, "Four N's and a C") before taking on the moniker Bobby Taylor & the Vancouvers.

In 1965, the Vancouvers signed with Gordy Records (a subsidiary of Detroit's Motown Records). They recorded their debut album, an eponymous release, and their debut single, the Tommy Chong co-composition, "Does Your Mama Know About Me," which peaked at number 29 on the Billboard Hot 100. While on tour in Chicago for a short time, the band followed opening act The Jackson 5. Chong later referred to the young Michael Jackson as a "cute little guy". After the band released two additional singles, Chong and Wes Henderson were fired by Clark and Motown producer Johnny Bristol for missing an appointment to apply for Green cards to enable them to live in the US. The group broke up shortly afterwards, when Chong tried to reduce the number of players covered by the Vancouvers' contract. He intended that he, Taylor, and Henderson would constitute the group, while other members would be classified as sidemen and session artists.

Chong co-wrote and performed on many Cheech & Chong comedy albums, two of which were nominated for Best Comedy Album Grammy Awards. He also directed four of the duo's films, while co-writing and starring in all seven with Cheech Marin.

Cheech & Chong, while a very successful comedy act, split in 1985 due to creative differences and Marin's desire to focus on a mainstream acting career. This began a difficult time for Chong. He did not act regularly until filling the recurring role (later a regular role) as the fun-loving, aging hippie "Leo" (similar to his Chong character) on That '70s Show. Chong was absent during the fifth and sixth seasons of the show as he was serving a brief jail sentence; upon his release, he returned to the series for its final two seasons. He also played a role as a hippie in Dharma and Greg.

Chong was originally going to voice the character of Shenzi, the hyena in the Disney film The Lion King. Cheech Marin voiced Banzai. (The Shenzi character was changed to a female, and voiced instead by Whoopi Goldberg.) Decades later, Chong would appear in a Disney animated film of his own, Zootopia, where he voiced a yak named Yax.

In September 2005, a/k/a Tommy Chong premiered at the Toronto International Film Festival. The documentary, produced, written and directed by Josh Gilbert, chronicles Chong's comedic and personal history. It includes material related to his prosecution by the US Justice Department and imprisonment. The project features interviews with Cheech Marin, Bill Maher, George Thorogood, Peter Coyote, Lou Adler, Eric Schlosser and Jay Leno. In 2011, Chong appeared as a Judge in an episode of Franklin & Bash.

On September 4, 2014, Chong was announced as one of the celebrities participating on the 19th season of Dancing with the Stars. He paired with professional dancer Peta Murgatroyd. Despite being at the bottom of the leaderboard numerous times, Chong and Murgatroyd were able to make it to the night of the semi-finals but were eliminated at the end of that night. Chong is the oldest contestant to have made it to the semi-finals of the show.

On April 4, 2015, Chong was in Ann Arbor, Michigan, for the annual "Hash Bash" event which focuses on cannabis legalization. He was a guest speaker at this event, took pictures with fans and signed autographs.