As a true freshman for Washington in 2014, Pettis had 17 receptions for 259 yards and a touchdown. He also added 288 punt return yards and a punt return touchdown.
As a sophomore, he recorded 30 receptions for 414 yards and a touchdown reception with 271 punt return yards and two punt return touchdowns.
As a junior, he finished with 53 receptions, 822 yards, 15 touchdown receptions, 287 punt return yards and two touchdowns.[4][5]
The San Francisco 49ers selected Pettis in the second round (44th overall) of the 2018 NFL draft.[12] He was the fourth wide receiver to be selected that year.[13] In the season-opener against the Minnesota Vikings, Pettis made his NFL debut and caught two passes for 61 receiving yards and a touchdown. In addition, he returned two punts for 14 yards in the 24–16 loss.[14] On December 29, 2018, Pettis was placed on injured reserve after suffering a knee injury.[15] Pettis finished his rookie season with 27 receptions for 467 yards and five touchdowns.[16]
In Pettis' second season, he caught 11 receptions for 109 yards and two touchdowns.
On November 3, 2020, Pettis was waived by the 49ers.[17]
New York Giants
On November 4, 2020, Pettis was claimed off waivers by the New York Giants.[18] He was placed on the reserve/COVID-19 list by the team on November 20, 2020,[19] and activated on December 1.[20]
In his first game played as a Giant, on December 27, 2020, against the Baltimore Ravens, Pettis finished with two receptions for 33 yards. He caught his first touchdown as a Giant the next week, against the Dallas Cowboys, for 33 yards. Pettis finished his 2020 campaign with four receptions, for 76 yards, averaging 19 yards a reception, and one touchdown.
On September 1, 2021, Pettis was waived by the Giants and re-signed to the practice squad.[21][22] On October 19, 2021, Pettis was signed to active roster.[23] In Week 7 against the Carolina Panthers, Pettis had five catches for 39 yards and a touchdown while adding the 16-yard pass to Daniel Jones.[24] On November 5. 2021, Pettis was placed on injured reserve with a shoulder injury.[25]
Chicago Bears
On May 11, 2022, the Chicago Bears signed Pettis.[26] On October 14, Pettis caught four passes for 84 yards and the Bears’ only touchdown, during a 12–7 loss to the Washington Commanders.[27]
Pettis re-signed with the Bears on April 17, 2023.[28] He was placed on injured reserve on August 26.[29] He was released on September 6, 2023, with an injury settlement.[30]
On March 15, 2024, Pettis re-signed with the Bears.[31] He was placed on injured reserve on August 27, and released a week later.[32]
New Orleans Saints
On October 15, 2024, Pettis signed with the New Orleans Saints practice squad.[33] On December 7, he was promoted to the active roster.[34]