Mazin began his entertainment career as a marketing executive with Walt Disney Pictures in the mid-1990s, where he was responsible for writing and producing campaigns for studio films.
He graduated magna cum laude with a degree in psychology from Princeton University in 1992. His freshman year roommate at Princeton was Ted Cruz, now the junior U.S. Senator from Texas and a former Republican candidate for the 2016 presidential election year. He has been highly critical of Cruz and ridicules him frequently from his Twitter account.
He made his screenwriting debut with 1997's sci-fi comedy RocketMan, co-written with then-writing partner Greg Erb. He has since written movies such as Senseless, Scary Movie 3, Scary Movie 4 and Identity Thief.
Mazin has directed two films: 2000's low-budget superhero film The Specials, which he also produced, and the 2008 superhero spoof Superhero Movie, which he also wrote.
Since 2006, Mazin has collaborated with Director Todd Phillips on several occasions. Mazin co-wrote both Hangover sequels, parts II and III, and executive produced School for Scoundrels.
Mazin was born in Brooklyn, New York, and raised on Staten Island, New York. He moved to Marlboro Township, New Jersey when he was a teen and attended Freehold High School which inducted him into its Hall of Fame in 2010.
In 2011, Mazin and fellow Screenwriter John August began Scriptnotes, a weekly podcast on the craft of screenwriting and the film industry.
In July 2017, HBO and Sky Television announced Chernobyl, a five-part miniseries from Mazin about the nuclear disaster at Chernobyl. The series will be filmed in Lithuania.