He played college football at Eastern Washington, where he won the Walter Payton Award as a junior, and was selected by the Rams in the third round of the 2017 NFL draft.

Kupp was also named by the Seattle Times as a "White Chip" selection, as one of the top 100 prospects in the state of Washington.

[4] Kupp was a unanimous first-team All-Columbia Basin Big Nine League wide receiver and defensive back at Davis.

Kupp also had 11 rushes for 122 yards and two touchdowns as he helped Davis come one game away from a berth in the Washington State 4A Playoffs.

[4] Kupp finished his prep career without a single college football scholarship offer[5] despite recording 110 catches for 2,100 yards.

He finished the season having set numerous single-season school and national receiving records at the Football Championship Subdivision Level.

[8] On December 16, 2013, Kupp was named the recipient of the 2013 Jerry Rice Award, given to the top freshman player in the FCS.

He was also named to the first-team All-Big Sky for the second straight year as a wide receiver while also earning third-team honors as punt returner.

Moreover, Kupp's 6,464 yards eclipsed Scott Pingel's all-division NCAA record set in 1999, which was accomplished at the Division III level of competition.

On March 28, 2017, Kupp opted to participate in Eastern Washington's pro day along with Jordan West, Shaq Hill, Samson Ebukam, Kendrick Bourne, and Miquiyah Zamora.

[47][48][49] Kupp competed with Tavon Austin, Robert Woods, Mike Thomas, Bradley Marquez, Pharoh Cooper, and Josh Reynolds throughout training camp for a starting wide receiver role left vacant after Kenny Britt departed in free agency.

[50] Head coach Sean McVay named Kupp the fourth wide receiver on the depth chart behind Watkins, Woods, and Austin.

[51] Kupp made his NFL debut in the season-opening 46–9 victory over the Indianapolis Colts and recorded four receptions for 76 yards, including an 18-yard touchdown pass from Jared Goff, marking the first of his career.

[54] Through the first seven games of the season, Kupp led the Rams in red-zone targets with 11 and developed as Goff's top receiver in the red zone and third downs.

[55] During a Week 9 51–17 victory over the New York Giants, Kupp made his first career NFL start, catching three passes for 54 yards.

[58] By December, Kupp was a full-time starter at wide receiver and ended his rookie season in 2017 with 62 receptions for 869 yards and five touchdowns in 15 games and six starts.

[62] Kupp was named a starting wide receiver in 2018 alongside Robert Woods and offseason acquisition Brandin Cooks.

[63] During a Week 4 38–31 victory over the Minnesota Vikings, Kupp caught nine passes for 162 yards and two touchdowns (all single-game highs), including a career-best 70-yard scoring reception.

[88][89] Kupp ended the season with a very productive six-game stretch from Weeks 13–18, averaging 118.3 yards per game and six total touchdowns.

[90] In the Rams' 12–5 season, Kupp set numerous franchise single-season receiving records, which resulted in Pro Bowl and First-team All-Pro honors.

[100] In the Divisional Round, he recorded nine receptions for 183 yards and a touchdown in the narrow 30–27 road victory over the Tampa Bay Buccaneers.

[102] In the NFC Championship Game against the San Francisco 49ers, he recorded 11 receptions for 142 yards and two touchdowns in the 20–17 victory, bringing the Rams back to the Super Bowl for the second time since 2018.

[109] In the NFL Kickoff Game against the Buffalo Bills, Kupp caught 13 passes for 128 yards and a touchdown in the 31–10 loss.

[127] Kupp opened the season against the Detroit Lions with 14 receptions, tying his career high, along with 110 yards and a touchdown as the Rams lost in overtime.

[132] The pair of scores vaulted Kupp past Hall of Famer Elroy Hirsch to third place for team career receiving touchdowns behind Bruce (84) and Holt (74).

[133] In a Week 15 matchup with the San Francisco 49ers, Kupp was held without a catch for only the third time in his professional career, a streak that had reached 69 consecutive games.

[135] On February 3, 2025, Kupp announced that the Rams' front office informed him that he was not in their future plans for the team and that they intended to trade in him in 2025 offseason.

[144] His younger brother, Ketner, also played at Eastern Washington and was signed by the Los Angeles Rams as a free agent in 2019, participating in training camp and in preseason games, but was released during the final roster cutdown.

[145] His grandfather, Jake Kupp, was an offensive lineman for the University of Washington and was selected in the ninth round of the 1964 NFL draft by the Dallas Cowboys.

[144] Kupp developed a close friendship with former Rams quarterback Jared Goff while living with him for a few weeks after the draft.