Pettis attended JSerra Catholic High School in San Juan Capistrano, California. He played football, basketball and ran track. As a senior in football, he had 50 receptions for 889 yards and 11 touchdowns. He committed to the University of Washington to play college football. 
As a true freshman at Washington in 2014, Pettis played in 13 of 14 games with five starts and had 17 receptions for 259 yards and a touchdown. He also added 288 punt return yards with a touchdown.
In 2015, he started eight of 13 games, recording 30 receptions for 414 yards and a touchdown with 271 punt return yards and two touchdowns.
As a senior in 2017 against the Oregon Ducks, he broke the record for most career punt return touchdowns in NCAA history.   Pettis garnered consensus All-America honors after being named a first-team All-American by the AFCA, FWAA, Walter Camp Football Foundation, and The Sporting News. 
His father, Gary Pettis, played in Major League Baseball (MLB) and is a coach for the Houston Astros.   His brother, Kyler Pettis, is an actor and his cousin, Austin Pettis, played in the NFL.