He played at Ole Miss for three seasons before declaring for the 2019 NFL draft, where he was selected by the Seahawks in the second round.

Metcalf's father, Terrence, also played college football at Ole Miss and was an offensive lineman in the NFL for the Bears, Lions and Saints.

[10] Metcalf was selected by the Seattle Seahawks in the second round as the 64th overall pick in the 2019 NFL Draft, the ninth of 28 wide receivers.

[15] Metcalf played his first regular season game on September 8, 2019, against the Cincinnati Bengals, where he made four receptions for 89 receiving yards as the Seahawks won 21–20.

In Week 2 against the Pittsburgh Steelers, Metcalf caught three passes for 61 yards, including his first career touchdown, as the Seahawks won 28–26.

[18] The following week against the Tampa Bay Buccaneers, Metcalf set new career highs in receptions and receiving yards, with six catches for 124 yards, including a 53-yard touchdown in the final minutes of the fourth quarter and a 29-yard catch on 3rd down in overtime that set up a game winning touchdown a few plays later.

[22] In the Wild Card Round against the Philadelphia Eagles, Metcalf recorded seven catches for 160 yards and a touchdown in the Seahawks' 17–9 victory.

[26] In the first quarter of the Week 3 game against the Dallas Cowboys, after catching a 61-yard pass, Metcalf slowed to a jog and held the ball out with one hand, seemingly unaware that a defender was behind him.

Trevon Diggs knocked the ball free of Metcalf's grasp before he broke the plane of the endzone, and the fumble traveled out of bounds for a touchback.

On their ensuing possession, Arizona failed to score, turning the ball over on downs after an incomplete pass from the 3-yard line.

[33] Metcalf reached a top speed of 22.64 mph (36.43 km/h), making it the second-fastest in pursuit in the NFL to that point in the season.

[34] Ironically, the play was also compared to Leon Lett's Super Bowl XXVII gaffe, yet this time in a far more favorable light.

[35] The play was met with awe by fans and athletes alike, and became the basis for a popular meme on social media.

[37] In Week 12 against the Philadelphia Eagles on Monday Night Football, he had ten receptions for a career-high 177 receiving yards during the 23–17 win.

[43] Earlier in the year before the start of the NFL season, he participated in the 100 meter part of the USATF Golden Games and Distance Open in Walnut, California.

[46] In another primetime matchup with Week 7's Sunday Night Football game against the New Orleans Saints, Metcalf caught 2 passes for 96 yards and a touchdown.

In addition, Metcalf clocked in at a top speed of 21.21 mph, making it the second-fastest play of his career as a ball-carrier.

[50][51] In Week 16, Metcalf caught six receptions for 63 yards and a career-high three touchdowns, contributing 18 points in a blowout 51–29 win against the Detroit Lions.

Metcalf emerged as a notable piece in the game's performance as he managed a touchdown during the second quarter to put the Seahawks up 13–7 by the half.

Beginning in December 2019, 16-ounce bags of coffee labeled "Decaf Metcalf" began selling on the company's website.