For King Crimson, he initially formed part of the "double trio" lineup of 1994, joining Bill Bruford on drums.
Mastelotto was born in Chico, California. He started playing the drums at the age of 10; by the time he was 16 he was playing in popular local bands and while still in high school commuted several hours to Lake Tahoe for gigs. Moving to Los Angeles in the mid 1970s, Mastelotto worked for many bands and as a studio session drummer. In this capacity he worked for Martin Briley, Holly Knight, Scandal, Al Jarreau, The Pointer Sisters, Patti LaBelle, Kenny Loggins, Martika, Danny Wilde as well as playing drums on the double platinum album Rockland by Canadian rock musician Kim Mitchell.
In 1983, Mastelotto was a founding member of Mr. Mister. The band had a number one album, Welcome to the Real World, and two number one singles, "Broken Wings" and "Kyrie". They recorded four albums, with the fourth, Pull, recorded in 1989–1990 but remaining unreleased until late 2010.
His tenure with Mr. Mister was followed by more session work for bands such as XTC, The Sugarcubes, Hall & Oates, Cock Robin, The Rembrandts, Jude Cole, Eddie Money, Tina Arena, Matthew Sweet, Julia Fordham, Robyn Hitchcock and David Sylvian. In 1991 Mastelotto co-produced Peter Kingsbery's first solo album before being asked to join King Crimson.
Mastelotto has been a member of King Crimson since 1994, and appears on over twenty King Crimson albums and several music videos. He also produced, edited mixed or played on several King Crimson ProjeKcts releases.
He has continued to guest on other projects, working with Jay Terrien, Cock Robin, drummer Terry Bozzio, Mecca, Herd of Instinct, Tony Levin and the California Guitar Trio, as well as working on solo work. He is also a member of the progressive/experimental bands TU (with fellow King Crimson alumnus Trey Gunn) and KTU (with Trey, Kimmo Pohjonen and Samuli Kosminen), and Tuner; a duo with centrozoon's Markus Reuter that has released four albums and toured periodically. That touring included Estonia in 2007 which was documented on a live album. On stage Tuner have been known to reinterpret King Crimson material such as the 1984 track 'Industry', as evidenced on their 2009 live album ZWAR.
Since moving to Austin, Texas, he has worked with Austinites Storyville, Abra Moore, ...And You Will Know Us by the Trail of Dead and theremin player Pamelia Kurstin. Personal projects include, Mastica, BPMM and M.P.TU with guitarist Phil Brown (Little Feat), singer Malford Milligan and bassist Mark Andes (Spirit, Firefall, Heart). He works as an executive producer, also producing, engineering, and mixing. He has appeared in major network television themes, and has worked in the studio on such projects. In 2007 Mastelotto went on tour with The Flower Kings in Europe supporting their album The Sum Of No Evil. In 2008 a new King Crimson lineup formed, including a drumming team of Pat and Gavin Harrison, which played eleven shows in August. Then the enormous Creation of Peace festival in Kazan, Russia, with Adrian Belew, Tony Levin and Eddie Jobson. This was followed by another new project, HoBoLeMa, with Levin, Bozzio and Allan Holdsworth. Pat also works with Reuter and Levin in the trio Stick Men who released their fourth album Deep in 2013. He is known for his production skills and technical ability while in the studio. Pat is often working the Digital Audio Workstation in the studio. He has produced a number of King Crimson releases, as well as Crimson-related side projects.
In 2014, he released a collaborative album with Tobias Ralph called ToPaRaMa.
In 2015, he released a collaborative album titled "Inflamed rides" with Carmelo Pipitone (guitarist of Italian band Marta sui Tubi), Lorenzo Esposito Fornasari (Berserk!, Obake) and Colin Edwin (Porcupine Tree).