South Florida Bulls quarterback Byrum Brown (17) looks on before the game Sept. 13, 2025, against the Miami Hurricanes at Hard Rock Stadium in Miami Gardens, Florida. Mandatory Credit: Sam Navarro-Imagn Images

Friday night in the American brings a chance to view one of the G5 College Football Playoff contenders in action from Tampa Bay as the South Florida Bulls host the Charlotte 49ers at Raymond James Stadium.

South Florida started the season with a bang, beating Boise State and Florida before running into a buzzsaw that is the Miami Hurricanes. Charlotte is seeking its identity as a 1-3 team that has struggled to find much success this season as they try to pull off a rather large upset.

If you are looking for some betting advice for the matchup, we've got you covered. Here are the latest odds for the game, courtesy of BetMGM.

Stream Charlotte vs. USF

Charlotte vs. USF game odds

All college football odds via BetMGM

  • Spread: USF -27.5 (-115), Charlotte +27.5 (-105)
  • Money Line: USF -10000, Charlotte +1850
  • Over-Under: Over 54.5 (-115), Under 54.5 (-105)

Charlotte vs. USF prediction, pick:

This one could get ugly and in a hurry. USF is simply the better team here and should be able to bully the 49ers in the Tampa humidity. Aside from Miami, USF has held opponents under 16 points in all three of its other games. Charlotte's offense lacks the firepower to show anything different.

USF QB Byrum Brown is a dual-threat who can hurt Charlotte through the air, as he has 983 passing yards and six touchdowns, as well as two more scores on the ground. The Bulls will control the tempo in this one and should be on cruise control early in the second half.

Prediction: USF 37, Charlotte 10

Best Bet: Under 54.5

Charlotte vs. USF channel, start time, streaming:

Time: 7 p.m. ET

TV Channel: ESPN2

Live Stream: ESPN App

Get more betting analysis and predictions at Sportsbook Wire.

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This article originally appeared on College Sports Wire: Charlotte vs. USF: Week 6 College Football Betting Odds, Prediction, Pick

Reporting by Riley Donald, College Sports Wire / College Sports Wire

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