Since becoming ACC divisional rivals Clemson is 4-0 straight up against Louisville, but only 2-2 against the spread, allowing the Cardinals to keep a couple games close as underdogs. Clemson is a huge favorite for Saturday afternoon's meeting with Louisville at Death Valley.
College football point spread: The Tigers opened as 37.5-point favorites, according to sportsbooks monitored by OddsShark. (Line updates and matchup report)
College football betting pick, via OddsShark computer: 52.3-5.2 Tigers (College football picks on every game)
Why the Louisville Cardinals can cover the spread
The Cardinals are a tough case to make at the moment, what with five losses in a row, including a 56-35 defeat at home to Wake Forest last week. Louisville actually took an early 7-0 lead on a long Trey Smith touchdown run but gave up the next 21 points of the game and never recovered. The Cardinals later fell down by 21, got back to within 14 twice but faded.
On the day Louisville accumulated 532 yards of offense, made 31 first downs and won time of possession by a 34/26 tilt. The Cardinals just couldn't stop the Demon Deacons' running game.
Three weeks ago Louisville only trailed a good Boston College team on the road 24-20 into the fourth quarter, before giving up the last 14 points in a 38-20 loss.
Why the Clemson Tigers can cover the spread
The Tigers reached 8-0 on the season and 3-0 ATS over their last three games by flooring Florida State last week 59-10, covering as 17-point favorites. Clemson started slowly, then scored four touchdowns in the second quarter for a 28-0 halftime lead. The Tigers later pushed that advantage to 45-0 before allowing the Seminoles to hit the board, on their way to the easy win/cover.
On the afternoon Clemson out-gained FSU 524-247. The Tigers have now out-gained every opponent this season except Texas A&M, and out-rushed every opponent except North Carolina State.
Clemson has also won its last three games by a combined score of 163-20, covering additional spreads of 20 and 18 points. The Tigers held steady at No. 2 in the polls this week, as they quest for another trip to the College Football Playoff.
Smart betting pick
Clemson is a national championship contender while Louisville is just terrible. However, the Tigers have what could be a big game at Boston College next week and will be tempted to rest starters once this game is in hand. And playing at home means the spread is inflated by at least a touchdown.
Meanwhile the Cardinals have not lost a game by 40 points in 10 years. It's not easy betting on a team that just lost to Wake Forest by three touchdowns but the smarter money here takes the points.
College football betting trends
Louisville is 0-4 SU in its last four games vs. Clemson.
The total has gone under in six of Clemson's last eight games at home vs. teams with losing records.
Louisville is 0-5 SU in its last five games vs. its conference.
All college football odds and betting trends according to Bleacher Report's official odds partner, OddsShark. Check out OddsShark on Twitter and Instagram or head to YouTube for more betting picks and analysis on this week's top games. You can also download the free odds tracker app.