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The winner of that matchup will stake its claim as the conference's best team and put itself in prime position for the College Football Playoff.
Here's a look at three top betting picks for Week 5 of the college football season:
Notre Dame (-11) vs. Syracuse (Sat, at 12 p.m. ET) - Matchup Report
This game does not have much luster as far as the national rankings go, but the Fighting Irish (1-3) find themselves in a bad spot and may just be a bad team. The Orange (2-2) can score with just about any team in the country, but how much is always the question. Syracuse has covered the spread in three of the past four meetings and will stay within double digits in this game at MetLife Stadium.
Wisconsin at Michigan (-10.5) (Sat, 3:30 p.m. ET) - Matchup Report
The Badgers are fresh off a dominant 30-6 road upset win at Michigan State, so the odds of them winning twice in as many weeks within the state seem very long. The Wolverines are at a completely different level when compared to the Spartans, and Wisconsin will find that out the hard way. Michigan is 9-2 straight up in its last 11 versus teams with winning records, and Jim Harbaugh's squad will rise to the occasion and win this one by more than two touchdowns.
Louisville (-2) at Clemson (Sat, 8 p.m. ET) - Matchup Report
The Tigers bring an 18-game home winning streak into this game against the Cardinals -- going 10-8 against the spread -- and they were not underdogs once during that stretch. While Louisville has looked mighty impressive this season behind Jackson, Clemson has won the past two meetings, including a 20-17 road victory last season, and will be very motivated to prove who is the better team and the better player (Watson) in pulling off the small upset.