[1] Defensive lineman Scott Patchan and punter Ryan Stonehouse were named to the Mountain West Football Preseason All-Conference Team.

One of the class's highest rated recruits, defensive back Branden Coleman, was a last-minute signing as he was previously committed to UCF and had not publicly shown interest towards Colorado State.

[9] 650 days after fans had last been present in Canvas Stadium, the Rams opened the 2021 football season on September 3, 2021, against the South Dakota State Jackrabbits in front of a crowd of 32,327.

Tight end Trey McBride led the team's receiving stats with eight receptions for 114 yards and a touchdown.

[14] On September 18, 2021, the Rams went on the road for the first time of the 2021 season and traveled to the Toledo Rockets' Glass Bowl for a Saturday afternoon game.

[16] Kicker Cayden Camper made five field goals on five attempts throughout the game to lead the Rams to their first win of the season, beating Toledo 22–6.

This interception set the Rams up for a quick touchdown drive before half and to everyone's surprise, Colorado State led Iowa 14–7 at halftime.

[18] Midway through the third quarter, Rams' running back A'Jon Vivens fumbled on his own six-yard line, setting Iowa up for an easy, one play touchdown drive that tied the game at 14.

[18] The Rams fell to 1–3 on the season with this loss, but spirits remained high as a result of the team's impressive performance.

[22] Head coach Steve Addazio's conservative, smashmouth offense was largely to thank for this — four of his six field goals were under 30 yards long, which resulted from the Rams' inability to score in the red zone.

At the 8:09 mark of the first quarter, Colorado State recorded their first interception of the game when cornerback Marshaun Cameron picked off Lobos quarterback CJ Montes on a badly underthrown pass.

[24] The Rams capitalized off of the interception and after a long drive, running back David Bailey scored a two-yard rushing touchdown with 2:57 remaining in the first quarter.

At the 6:01 mark of the third quarter, Lobos quarterback CJ Montes fumbled the snap, and Rams senior linebacker DeQuan Jackson recovered it.

[24] The fourth quarter opened with a 50-yard pass to Rams tight end Trey McBride, which set up Camper to make a 25-yard field goal.

On Colorado State's next drive, quarterback Todd Centeio completed a 43-yard pass to tight end Gary Williams for a touchdown, making the score 33–7.

On New Mexico's responding drive, quarterback CJ Montes recorded his third turnover of the day, throwing an interception at his own 12-yard line.

[28] CSU's defense forced a punt on Utah State's responding drive to regain possession with just under a minute left in the game.

On CSU's next drive, quarterback Todd Centeio completed a 30-yard pass to tight end Cameron Butler for a touchdown.

On the Rams' final drive of the quarter, they settled for an even shorter, 20-yard field goal from Cayden Camper after failing to score from Boise State's two-yard line.

Colorado State ended the third quarter with a fourth and final sub-30-yard Cayden Camper field goal, highlighting the team's inefficiency in the red zone.

The two teams exchanged passing touchdowns in the fourth quarter to end the game; the final score was 31–17 in favor of the Cowboys, who won the Bronze Boot back from Colorado State.

[37] Colorado State opened the game with a quick three-and-out, and Air Force responded by scoring a touchdown on their first drive.

Air Force promptly responded, scoring a touchdown on a 92-yard pass from quarterback Haaziq Daniels to wide receiver Brandon Lewis to bring the score to 21–7 at the end of the first quarter, which broke the record for the longest pass in Air Force school history.

The second quarter began with a Cayden Camper field goal at the 12:35 mark; Hawaii responded with a rushing touchdown to bring the score to 16–10 in their favor.

Quarterback Todd Centeio had the best statistical game of his Colorado State career, completing 29 passes on 48 attempts for 527 yards, five touchdowns and two interceptions.

[41] On November 27, 2021, the Nevada Wolf Pack traveled to Fort Collins to play the Rams in their final game of the 2021 season.

[43] Nevada scored two first-quarter touchdowns — both from quarterback Carson Strong to wide receiver Tory Horton — to go up 14–0 at the end of the quarter.

Colorado State finally got on the scoreboard with around a minute into the second half, when tight end Trey McBride took a fake punt run 69 yards for a touchdown.

[44] Colorado State lost their sixth consecutive game, losing the entire back half of the season to finish with a 3–9 record.

Quarterback Todd Centeio finished his final game at Colorado State by completing 15 of 24 passes for 185 yards, no touchdowns and two interceptions.