[14] He made his NFL debut in the Seahawks' 27–24 loss to the Denver Broncos in the season opener.

[15] In a Week 10 loss to the Los Angeles Rams, Penny had a breakout game with 12 carries for 108 yards and a touchdown.

[19] During Week 12 against the Philadelphia Eagles, Penny finished with 129 rushing yards and a touchdown as the Seahawks won 17–9.

[27] The Seahawks declined to exercise the fifth-year option on Penny's contract on May 3, 2021, making him a free agent after the 2021 season.

[30] In Week 14, Penny had a breakout game rushing 16 times for 137 yards and two touchdowns in a 33–13 win over the Houston Texans.

[32] In Week 17, Penny ran for 170 yards on 25 carries along with two touchdowns in a 51–29 win against the Detroit Lions, continuing his breakout set of games.

[35] Overall, Penny played in ten games rushing for 749 yards on 119 attempts, and six touchdowns, all career highs.

[41] He was originally seen as a replacement for running back Miles Sanders, who departed for the Carolina Panthers in free agency over the offseason.

However, later in the offseason, the Eagles acquired D'Andre Swift from the Detroit Lions in a trade, and leading up to the 2023 season, Eagles head coach Nick Sirianni would not announce a starting running back, instead planning for a "committee approach" to the position, where Penny, Swift, Kenneth Gainwell, and Boston Scott would share carries.

[42] Despite this, Penny would end up seeing the least playing time, only appearing in three games throughout the season with 11 carries and a total of 33 yards.