He played in the NFL as a running back and on special teams with New England Patriots from 1978 to 1990 and the Los Angeles Rams in 1991.
The Mosi Tatupu Award , given annually to the College Football Special Teams Player of the Year by the Maui Quarterback Club and the Hula Bowl, bears his name.
However, the Patriots were terrible late in his career (they went 1–15 in his final season) and his playing time was sharply reduced in his final three years with the team; in one instance, Chris Berman mined humor from a blowout New England loss by showing all 13 receptions by Tatupu in the game, because none of the catches produced a touchdown or even a first down.
Tatupu was the head coach at King Philip Regional High School in Wrentham, Massachusetts from 1995 to 2001, compiled a record of 29–43 in seven seasons.
In 2014, using brain tissue preserved from his 2010 autopsy, he was posthumously diagnosed with chronic traumatic encephalopathy by the CTE Center at Boston University School of Medicine.
During the segment, the chief of Ape Island is shown to say "Mosi Tatupu, Mosi Tatupu", which in their language means "the blue-haired woman will make a fine sacrifice"—the "blue-haired woman" being Marge Simpson, who is playing Fay Wray's Ann Darrow to Homer's King Kong.