Chase attended Archbishop Rummel High School in Metairie, Louisiana, located in suburban New Orleans.

[8] His 20 receiving touchdowns set a Southeastern Conference (SEC) record until it was broken by DeVonta Smith the following year.

[20] Despite early struggles in the preseason,[21] Chase played his first career regular season game on September 12, 2021, against the Minnesota Vikings, finishing with 102 receiving yards and a touchdown as the Bengals won 27–24 in overtime.

[23] Chase was named the NFL Rookie of the Month for September after totaling 220 receiving yards and four touchdowns through his first three games.

[24] During the Bengals' 25–22 overtime loss to the Green Bay Packers, Chase had 159 yards, including a 70-yard touchdown at the end of the first half, earning him another Rookie of the Week award.

[29] In Week 17, against the Kansas City Chiefs, Chase totaled 266 receiving yards and three touchdowns during the Bengals' 34–31 division-clinching win.

[43] In Week 1, against the Pittsburgh Steelers, Chase caught ten passes for 129 yards and a game-tying touchdown with no time left in regulation, in the 23–20 overtime loss.

[44][45] In Week 6, Chase had his best performance of the season, making seven receptions for 132 yards and two second-half touchdowns in a 30–26 comeback victory against the New Orleans Saints.

[47] Chase still played the following week against the Atlanta Falcons where he had another two-touchdown game, finishing with 130 yards and eight receptions in the Bengals 35–17 win.

Chase began the season with a combined 70 yards on ten receptions in the Bengals' Week 1 and 2 losses to the Browns and Ravens.

[54][55] He bounced back in Week 3 on Monday Night Football against the Los Angeles Rams, with 12 receptions for 141 yards in the 19–16 win.

[57] Chase responded the following week against the Arizona Cardinals by delivering his second best personal performance to date, with 192 yards and three touchdowns on 15 receptions, setting a new Bengals franchise record for single-game receptions, which was previously set by Carl Pickens in Week 6 of the 1998 season; the Bengals went on to win 34–20.

[60] Chase injured his back during the Bengals' Week 9 victory over the Buffalo Bills on an awkward landing after an attempted diving catch.

[62] In Week 13 against the Jacksonville Jaguars, Chase pulled in 11-of-12 targets for 149 yards, his second best performance of the season, with a highlight of a 76-yard touchdown during the first drive of the second quarter of the 34–31 win.

After an MRI, Chase's injury was found to be significantly worse, leading him to miss the following week's game against the Pittsburgh Steelers.

[69] Chase had a highly publicized "hold-in" during the team's training camp, in hopes that the Bengals would sign him to an extension.