The 49ers played their home games at Jerry Richardson Stadium in Charlotte, North Carolina, and competed in the East Division of Conference USA (C–USA).
[1] On February 2, Texas co-offensive coordinator and offensive line coach Herb Hand was named to the same position at Charlotte.
[8] On June 30, Tyler Hancock joined the staff as special teams coordinator after working as a senior analyst for West Virginia.
Defense: DE – Markees Watts, R-Sr. • LB – Tyler Murray, R-Sr. Special Teams: KR – Shadrick Byrd, R-Fr.
The radio announcers are "Voice of the 49ers" Matt Swierad with play-by-play alongside NFL veteran Al Wallace providing color commentary and Bobby Rosinski and Walker Mehl with sideline reports.
[26] Conference USA released their preseason media poll on July 19, 2021, with the 49ers predicted to finish in fourth place in the East Division.
[27] Following the previous year's drubbing in Durham, the 49ers were looking to regain their pride against the Blue Devils in the first full stadium home game since the 2019 season.
Reynolds would then orchestrate a seven-play drive downfield that resulted in an eleven-yard touchdown pass to Shadrick Byrd with only thirty-three seconds left on the clock.
With time expired Duke attempted a hook-and-ladder play, but the 49ers would stop it cold and gain their first victory over a Power 5 and ACC opponent in program history.
Game notes: The 49ers were looking to build off of the previous week's success by dominating local rival Gardner-Webb Runnin' Bulldogs.
Charlotte's bend-but-don't-break defense allowed GWU to move the ball down the field but was able to frustrate most of the Runnin' Bulldogs' scoring attempts as the 49ers walked away with a 38 to 10 home victory.
Game notes: Rain and slick conditions would help turn this matchup into a ground and pound event dominated be defense.
The Illini would finally find the endzone with less than three minutes left in the half only to have the 49ers answer with a touchdown of their on to take a 14 to 10 lead into the halftime.
Charlotte would get into comfortable field goal range in the last seconds of the quarter to attempt to tie the game only to have the ball drift wide right.
Charlotte would stretch the lead out to 18 early in the 2nd half, but two plays later FIU would find the endzone for the first time in the game.
With less than six minutes left on the clock the 49ers again would go out to an 18 point lead on a Jon Alexander interception return, only to have the Panthers score on the very next play.
The Panthers looked like they might have recovered the ensuing on-sides kick, but the ball didn't cross the 10 yard mark by mere inches.
FIU would get it to within 12 points with less than 15 seconds on the clock, but the on-sides kick attempt this time was easily recovered by the 49ers who would leave Miami with a 45 to 33 win.
Top performers of the game included Florida Atlantic quarterback N'Kosi Perry, who threw for 225 yards and three touchdowns.
Game notes: In a light rain the 49ers struggled behind backup quarterback James Foster to establish an offensive rhythm.
The second half would be significantly less active, but it was all Hilltoppers, adding two more touchdowns and a field goal to put the game safely in their pocket.
Top performances of the game were dominated by the Hilltopper's, whose Bailey Zappe threw for 393 yards, 4 touchdowns and 2 interceptions on his way to collecting a CUSA Offensive Player of the Week Award.
With less than a minute and a half left in regulation Chris Reynolds would find Elijah Spencer in the corner of the endzone to tie the game for the second time.
Once again Charlotte experienced a second half change in pace as the Bulldogs early in the third quarter took a commanding two score lead.
The Herds' Corey Gammage had 3 receptions for 78 yards and a touchdown Game notes: Both teams in this contest need the win to become bowl eligible.
Old Dominion dominated the top performances of the game with Hayden Wolff throwing fir 328 yards, 3 touchdowns and 2 interceptions.