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College Football Week 5 opening lines, odds and best bet: Irish cruise in South Bend

College Football Week 5 opening lines, odds and best bet: Irish cruise in South Bend

Sam Avellone
Sam AvelloneAuthor
UpdatedApr 29, 2026
Reading time4 min

With a healthy number of blowouts across the college football landscape, Week 4 wasn’t exactly the most ideal viewing experience from a competitive standpoint. However, underdogs piqued interest heading into the weekend with a perfect 4-0 ATS mark on Thursday and Friday, and there were a few notable outright winners on Saturday including James Madison, Michigan, Utah, Rutgers, Navy and BYU.

Now that college football Week 4 is behind us, focus shifts to Week 5. It’s a smaller slate with ample teams on bye, but there are 4 notable ranked matchups headlined by the Georgia Bulldogs’ trip to Tuscaloosa to play the Crimson Tide. Oddsmakers already posted the lines for the week ahead, and some of them quickly moved off the opening number. Let’s take a look at where they settled at the time of publishing on Sunday night, and cap it off with an early week best bet.

Make sure you check Pickswise throughout the week for picks on all the biggest college football games in Week 5. 

NCAAF Week 5 opening lines and odds

Odds courtesy of Bet365 at the time of publishing.

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  • Army -13 (-110) @ Temple – Thursday, September 26
  • Miami -17 (-110) vs Virginia Tech – Friday, September 27
  • Rutgers -2.5 (-110) vs Washington – Friday, September 27
  • Texas Tech -3.5 (-110) vs Cincinnati – Saturday, September 28
  • UCF -14 (-110) vs Colorado – Saturday, September 28
  • Ole Miss -17.5 (-110) vs Kentucky – Saturday, September 28
  • Indiana -7 (-110) vs Maryland – Saturday, September 28
  • Nebraska -10 (-110) @ Purdue – Saturday, September 28
  • NC State -7 (-110) vs Northern Illinois – Saturday, September 28
  • Kansas State -5.5 (-110) vs Oklahoma State – Saturday, September 28
  • Kansas -2 (-110) vs TCU – Saturday, September 28
  • Texas A&M -4.5 (-110) vs Arkansas – Saturday, September 28
  • Baylor -3 (-110) vs BYU – Saturday, September 28
  • Penn State -17.5 (-110) vs Illinois – Saturday, September 28
  • Liberty -3.5 (-110) @ Appalachian State – Saturday, September 28
  • Notre Dame -5 (-110) vs Louisville – Saturday, September 28
  • Michigan -10 (-110) vs Minnesota – Saturday, September 28
  • Oklahoma -3 (-110) @ Auburn – Saturday, September 28
  • USC -14 (-110) vs Wisconsin – Saturday, September 28
  • Duke -3 (-110) vs North Carolina – Saturday, September 28
  • Georgia -2 (-110) @ Alabama – Saturday, September 28
  • SMU -5.5 (-110) vs Florida State – Saturday, September 28
  • Ohio State -24.5 (-110) @ Michigan State – Saturday, September 28
  • Boise State -7 (-110) vs Washington State – Saturday, September 28
  • Utah -12.5 (-110) vs Arizona – Saturday, September 28

We’ll have NCAAF best bets for Week 5 posted throughout the week!

Best early bet for college football Week 5

Notre Dame Fighting Irish -5 (-110) over Louisville Cardinals

Coming out of their bye week, the Louisville Cardinals were out-gained at home by Georgia Tech 410-332. The Cardinals converted only 2 of their 9 3rd downs, averaged just 2.6 yards per carry and were penalized 7 times for nearly 70 yards – yet they managed to win and cover thanks to a blocked field goal in the middle of the 4th quarter that was returned 55 yards for a touchdown. With an unblemished 3-0 SU record, they will hit the road for the first time when they travel to South Bend, Indiana for a matchup with a ranked Notre Dame Fighting Irish (3-1) squad that has already been through quite a bit this year. The Irish won on the road at Texas A&M and immediately followed it up with an unexplainable home loss to Northern Illinois. However, they have recovered with 2 straight wins, holding Purdue and Miami (OH) to just 10 combined points in those victories. 

With a defense that is top 6 nationally in DFEI and PPA, Notre Dame represents a massive step up in class for the Louisville offense. The Cardinals have yet to play a FBS defense in the top 80 in either of those defensive efficiency metrics, so I expect their offense to come back to Earth a bit in South Bend on Saturday. Considering we have yet to see Louisville face much adversity this season, I don’t trust them to finish drives efficiently against this Notre Dame defense that yields less than 2.3 points per opposing scoring opportunity. This is a profitable spot for the Irish as favorites in a ranked non-conference matchup early in the season, so I’m taking Notre Dame now before the spread creeps up to key numbers of 6 and 7. 

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