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.