[1][2][3] Hopkins attended D. W. Daniel High School in Central, South Carolina, where he played football, basketball, and ran track and field for the Lions athletic teams.

[6] His senior season, 2009–10, the Lions won their third South Carolina State Championship,[7] and Hopkins was named the Independent Mail's player of the year.

[16] In the 2010 Meineke Car Care Bowl against South Florida, he had nine receptions for 105 receiving yards in the 31–26 loss to close out his freshman season.

Dating back to the prior season, this gave Hopkins three consecutive games with 100 receiving yards, tying a school record.

[43][44][45] Hopkins, along with junior quarterback Tajh Boyd and wide receiver Sammy Watkins, combined to make one of the most prolific passing offenses in college football and broke many individual and career school records.

[49] Hopkins attended private workouts or visits with the Dallas Cowboys, Carolina Panthers, New England Patriots, and had two with the St. Louis Rams.

[71] Hopkins returned as a starting wide receiver alongside Andre Johnson under new head coach Bill O'Brien to begin the 2014 season.

[78] Hopkins was solidified as the Texans' number one receiver to begin the 2015 season after veteran Andre Johnson departed to the Indianapolis Colts in free agency.

[80] Two weeks later, he recorded his first 100-yard receiving game of the season, with eight receptions for 101 yards and a touchdown in a 19–9 victory over the Tampa Bay Buccaneers.

[83][84] During Week 13 against the Buffalo Bills, Hopkins broke the Texans' franchise record for most touchdown receptions in a season, which was formerly held by Andre Johnson,[85] with his tenth score.

In the 2015 season, his usage increased to 192 targets, which ranked third among NFL wide receivers, trailing only Antonio Brown of the Steelers and Julio Jones of the Falcons.

[86][87] Hopkins finished the 2015 season with then-career highs in receptions (111), receiving yards (1,521), and touchdowns (11), despite playing with four different quarterbacks (Brian Hoyer, Ryan Mallett, T. J. Yates, and Brandon Weeden).

[92] In the 2016 season, Hopkins suffered through some small regression as the quarterback play of Brock Osweiler lacked positive consistency.

[98][63] During the season-opening 29–7 loss to the Jaguars, Hopkins caught the first NFL touchdown pass of quarterback and fellow Clemson Tiger Deshaun Watson's career.

[100] During Week 8 against the Seattle Seahawks, Hopkins posted an impressive performance with eight receptions for 224 receiving yards, which was highlighted by a 72-yard touchdown.

[115] In the Wild Card Round against the Colts, playing with a torn ligament in his shoulder, he finished with five receptions for 37 yards in the 21–7 loss.

[129] In the Wild Card Round against the Bills, Hopkins recorded six receptions for 90 receiving yards and a crucial two-point conversion in a 22–19 overtime victory.

On the Texans' final drive in overtime, Hopkins had a key first down early to set in motion the eventual game-winning field goal.

[137] On September 13, 2020, Hopkins made his debut as a Cardinal against the San Francisco 49ers, recording a career-high 14 receptions for 151 yards in the 24–20 win.

[138] In Week 2 against the Washington Football Team, Hopkins caught eight passes for 68 yards and his first receiving touchdown as a Cardinal during the 30–15 win.

[141] In Week 7 against the Seahawks on Sunday Night Football, Hopkins recorded 10 catches for 103 yards and a touchdown during the 37–34 overtime win.

[145] On November 19, Hopkins became the youngest player to reach 700 catches, a record that was held by his teammate, Larry Fitzgerald,[146] during the 28–21 loss to Seattle.

[154] On October 24, a Week 7 game against his former team the Texans, Hopkins caught seven passes for 53 yards and a touchdown in the 31–5 win for the eighth straight defeat and a perfect 7–0 record.

[155] After the Thursday Night Football loss to the Green Bay Packers, 24–21, Hopkins missed the next three weeks with a hamstring injury.

[171] Three days after being traded, Hopkins made his Chiefs debut on October 27 against the Las Vegas Raiders, catching two passes for 29 yards.

[174] He reached the Super Bowl for the first time in his career, scoring a touchdown and a two-point conversion in the 40–22 loss to the Philadelphia Eagles.

Because of her inability to watch him play due to blindness, Hopkins started a tradition of giving touchdown balls to her immediately after scoring in an effort to remain close to her.

[180][181] Hopkins' uncle on his mother's side, Terry Smith, played wide receiver at Clemson and went undrafted before having a brief professional career.

The partnership started the Feed A Million+ pledge with the intent to donate and distribute more than one million Beyond Burgers across the United States to needy people.

[187] In 2020, Hopkins displayed the name of Denmark Vesey on his helmet as a tribute to the alleged mastermind of a thwarted 1822 South Carolina slave revolt.