Born in Lagos, Nigeria, Agholor moved to the United States when he was five years old. He attended Berkeley Preparatory School in Tampa, Florida where he played running back, wide receiver, and defensive back for the Berkeley Buccaneers. He was rated by Rivals.com as a five-star recruit and was ranked as the third best wide receiver in his class. He committed to the University of Southern California in January 2012 over Notre Dame, Oklahoma, Florida, Florida State, and Alabama.

As a true freshman in 2012, Agholor played in all 13 games as a backup wide receiver and recorded 19 receptions for 340 yards and two touchdowns.

As a sophomore in 2013, he became a starter. Agholor started all 14 games, totaling 56 receptions, 918 yards, and six touchdowns as a receiver. Along with being the leading receiver, Agholor returned punts and kicks for the Trojans. He returned 18 punts for 343 yards and two touchdowns, and 10 kickoffs for 175 yards. Agholor was recognized as a second-team All-American by numerous sports outlets for his punt returning. Agholor returned as a starter his junior season in 2014. He led the team with 104 receptions for 1,313 yards and 12 touchdowns.

Agholor was selected by the Philadelphia Eagles in the first round with the 20th overall pick of the 2015 NFL Draft. He signed a four-year contract on May 7, 2015, worth around $9.4 million with a signing bonus of $5.1 million.

On December 13, 2015, Agholor scored his first NFL career touchdown, a 53-yard reception from quarterback Sam Bradford, in a matchup against the Buffalo Bills. During his rookie season in 2015, Agholor played 13 games with 283 receiving yards and a touchdown.

During his second season in 2016, Agholor played 15 games with 365 receiving yards and two touchdowns.

On March 13, 2017, it was reported that Agholor would switch from the #17, which he wore in his first two seasons, to the #13. He opted to give the #17 to newly acquired free agent wide receiver Alshon Jeffery.

During the 2017 season, Agholor found more success when he was switched to a slot receiver role. On September 10, 2017, in the season opening 30–17 victory over the Washington Redskins, Agholor had a 58-yard receiving touchdown from quarterback Carson Wentz in the first quarter. He finished the game with six receptions for 86 yards. On September 17, in a Week 2 27–20 loss to the Kansas City Chiefs, he recorded his second touchdown of the season late in the fourth quarter to cut into the Chiefs’ lead. He would end the 2017 regular season with his best season yet, getting more receiving yards and touchdowns than his previous two seasons combined.

On April 30, 2018, the Eagles exercised the fifth-year option on Agholor’s contract in order to retain him for the 2019 season.

In the 2018 season opener, against the Atlanta Falcons, Agholor completed his first career NFL pass attempt to Nick Foles on a trick play that went for 15 yards. The play helped set up an eventual Jay Ajayi-rushing touchdown in the Eagles’ 18–12 victory. In the next game, he scored his first receiving touchdown of the 2018 season as part of an eight-reception, 88-yard performance against the Tampa Bay Buccaneers. He put his best statistical performance of the season in the Week 16 32–30 victory over the Houston Texans with five receptions for 116 yards and a touchdown. Overall, in the 2018 season, he finished with 64 receptions for 736 yards and four touchdowns.

On March 25, 2020, Agholor signed a one-year contract with the Las Vegas Raiders.