The ACC for once has the premier game of college football’s conference championship weekend, aided by LSU’s upset at Florida and some schedule meddling by the league office that ensured its top two teams reached the title matchup. No. 2 Notre Dame and No. 4 Clemson will reprise their November classic in South Bend, a 47-40 Irish victory in double overtime.

Of course, there will be some differences this time around: most notably the Tigers will have star quarterback Trevor Lawrence, who missed the first game against the Irish while recovering from the coronavirus. Clemson will also have the use of three defensive starters who missed the trip to South Bend, so this will be a far more complete Tigers squad taking the field Saturday in Charlotte.

Notre Dame covered as a 7.5-point home underdog in the first game, and thanks to overtime the over/under well exceeded the total of 51.5. This time around, the Tigers are double-digit favorites at a neutral site. Here are your best bets on college football betting’s biggest game this week.

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Best Clemson vs. Notre Dame Betting Lines & Picks

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Clemson vs Notre Dame Spread Pick

Notre Dame has been good to spread bettors as of late, covering four of its last six – a stretch which includes the victory over Clemson. The Tigers, meanwhile, have been all over the place, regardless of which quarterback is behind center. Clemson is 4-6 against the spread this season and has covered just two of its last six.

No question, Lawrence’s return makes this a much taller hurdle for the Irish, but that Notre Dame defense is very good, as we saw in how it dominated the line of scrimmage and bottled up Clemson tailback Travis Etienne when the teams met the first time. And remember, Clemson backup quarterback D.J. Uiagalelei passed for 439 yards – most ever against the Irish, who still won the game.

Clemson has the star power, but Notre Dame is solid everywhere. Don’t underestimate the Irish a second time. We got them at +10.5 with PointsBet.

Clemson vs Notre Dame Moneyline Pick

Yet Notre Dame had a lot of factors break its way in the first meeting, from Clemson’s missing starters to a stunningly large and loud crowd at Notre Dame Stadium. None of those factors will be present Saturday. Both teams are playing very well as of late, routinely blowing out lower-rung ACC opponents over the final weeks of the regular season.

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It comes down to this, though: It took everything Notre Dame had to win at home against a Clemson team missing its starting QB and several defensive starters. It’s difficult to envision the Irish replicating that feat with Lawrence behind center for the Tigers, and the game being played at a neutral site. We jumped on Clemson at -400 with BetMGM.

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Clemson vs Notre Dame Totals Betting

Both teams have gone over the total six times in 10 games this season, and both are going over routinely as of late. Notre Dame has gone over in three of its last four, while Clemson had a string of five straight snapped in its most recent game, a 45-10 victory at Virginia Tech against a 66-point line. Clemson during that span also twice exceeded totals greater than 60 points.

Although the Tigers and Irish have both rolled up points against a lot of inferior ACC opponents, Clemson with Lawrence behind center is one of the most explosive teams in the nation. Irish quarterback Ian Book makes winning plays and has a bevy of good backs and tight ends. We like the over, and Clemson, in the neighborhood of 34-28. We took the Over at 60.5 with DraftKings.

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