Outside of the standup world, he is known for his co-starring roles in the film Night School, Showtime's dark comedy I'm Dying Up Here, NBC's About A Boy, as well as CBS sitcoms Broke, Gary Unmarried and Welcome to The Captain.

He grew up in San Francisco's Inner Sunset District, where his neighbors included future comedians Mike Pritchard and Margaret Cho.

[6][7][8] He attended Ecole Notre Dame Des Victoires,[9] a private Catholic school in San Francisco that emphasizes instruction of French language and culture.

Madrigal worked for 10 years in a human resources staffing agency run by his family, where one of his main responsibilities was firing people.

[12] Madrigal's stand-up comedy is story-based, centering on his personal life, family, and the confusion caused by his multiethnic background.

[14][15] Madrigal began his career in San Francisco's comedy clubs, both as a solo performer and as a member of the sketch group Fresh Robots, which he co-founded.

The show, which is based on William Knoedelseder's nonfiction book of the same name, is executive produced by Jim Carrey.

Madrigal and Lowitt performed a piece at Carolines on Texas Representative Debbie Riddle, who proposed a bill that would create state punishments for those who "intentionally, knowingly, or recklessly" hired unauthorized immigrants except for domestic workers.

[32][15] The network was started out by comedians Al Madrigal and Bill Burr with The Daily Show on the All Things Comedy website.

[33] The network was established as an artist owned cooperative, which Madrigal and Burr emphasize as an important aspect of the collective.

[42] At South by Southwest 2015, Madrigal, Burr, and comedian Doug Benson spoke on the "Owning Your Work: The Future of All Things Comedy" panel, where they "discussed the ins and outs of their operation and how they are working to help comics carve out their own paths in show business and avoid traditional gatekeepers.

"[42] From 2010 to 2014, he co-hosted a podcast called "Minivan Men" with comedians Maz Jobrani, Aaron Aryanpur, and Chris Spencer, in which they discussed marriage, parenting, and domestic issues.

The podcast has featured comics including Sinbad, Nick Thune, Felipe Esparza, Doug Benson, Pete Holmes, Ian Edwards, and Fred Stoller.

[3] Madrigal's fascination with superheroes and passion for increasing the representation of Latinx stories, characters, and voices led him to create and write the comic book series Primos in 2022 with publisher AWA and former Marvel Editor in Chief Axel Alonso and artist Carlo Barberi.

[5] Primos brings together three distant cousins, bound together by their ancient spacefaring Maya lineage to the historical King Janaab, with a profoundly special purpose: to save the world as they know it.

Returned to Earth, only to find their culture and civilization destroyed, one of the brothers vows revenge and seeks to decimate the planet with intergalactic technology gathered on his travels.

To prevent this, his sibling creates a contingency plan that activates the world's protectors – descendants of their own Pacal family.