Louisville Cardinals vs. Clemson Tigers Betting Odds, College Football Pick

Clemson is 2-0 against Louisville in the two meetings since the latter joined the ACC but 0-2 against the spread, as the Cardinals have given the Tigers two tough games.

Bettors might expect more of the same when the teams meet for a huge conference showdown—with national championship implications to boot—on Saturday night at Death Valley.

Point spread: The Tigers opened as 3.5-point favorites, according to sportsbooks monitored by Odds Shark (line updates and matchup report).

College football pick, via Odds Shark computer: 42.0-37.0 Cardinals (college football picks on every game)

Why the Louisville Cardinals can cover the spread

Louisville is not only 4-0 SU and 3-0-1 ATS on the season after winning at Marshall last week 59-28, but it also looks like a College Football Playoff contender with its own bone fide Heisman Trophy candidate.

One week after roasting Florida State, the Cardinals started a bit slowly against the Thundering Herd, leading just 7-0 after the first quarter, but they scored touchdowns on three straight possessions in the second quarter to open things up. Louisville eventually led 52-7 but let Marshall score three times in the fourth quarter—including the last with just under three minutes to go—to settle for a push as 31-point favorites.

On the evening, the Cardinals tripled up on the Herd in total yardage at 690-207, as sensational sophomore quarterback Lamar Jackson threw for 417 yards and five touchdowns. He's now accounted for 25 total touchdowns this season—12 on the ground and 13 through the air.

The 59 points Louisville scored last week was its lowest total so far this season.

Why the Clemson Tigers can cover the spread

Clemson is also 4-0 after taking out Georgia Tech last Thursday 26-7, covering as a 10-point favorite on the road. The Tigers drove 75 yards to a touchdown on their first possession of the game, led 14-0 after one quarter and 23-0 at the half, and they didn't allowed the Yellow Jackets to hit the board until less than 14 minutes remained.

On the night, Clemson outgained the Wreck 442-124, as the Tigers defense held the Tech option offense to just 95 yards rushing.

Clemson's own Heisman Trophy candidate, quarterback Deshaun Watson, put on his best performance so far this season, hitting on 32 of 48 throws for 304 yards and two touchdowns.

The Tigers own an 18-game winning streak at Memorial Stadium, going 10-5-3 ATS in the process.

Smart pick

There's something to be said about betting a hot hand, and nobody is hotter right now than Jackson and the Cardinals. Also, Louisville lost to the Tigers by a field goal last year and by two yards two years ago. For what should be another close contest, the Cardinals look like the smart call.

Betting trends

Clemson is 18-0 SU in its last 18 games at home.

The total has gone over in eight of Louisville's last nine games.

Louisville is 4-0 SU and ATS in its last four games after consecutive wins.

All college football betting lines and point-spreads data courtesy of Bleacher Report’s official odds partner, Odds Shark. All quotes gathered firsthand unless otherwise noted. Check out Twitter for injury and line-movement updates and Odds Shark YouTube for picks and analysis, or download the free odds-tracker app.