Opening College Football Week 4 Odds, Spreads and Early Predictions

• West Virginia vs Virginia Tech kicks off Week 4 of the college football season Thursday night
• Clemson vs Wake Forest is a key ACC matchup Saturday
• A look at all college football Week 4 odds can be found below, including point spreads and game totals

Week 4 of the 2022 college football season kicks off Thursday night (Sep. 22) with West Virginia vs Virginia Tech.

There will be three matchups involving ranked teams on Saturday with #5 Clemson vs #18 Wake Forest in the ACC and #20 Florida vs #11 Tennessee and #10 Arkansas vs #23 Texas A&M in the SEC.

The table below shows the Week 4 opening lines. See the college football odds during the week for updated odds and point spreads.

College Football Week 4 Opening Odds

Odds as of September 18th at DraftKings Sportsbook. Claim the DraftKings Sportsbook promo code. 

The biggest favorites on the board are NC State (vs UConn) and Alabama (vs Vanderbilt). Both are 40-point chalk in the opening Week 4 odds.

Oddsmakers expect a handful of games to be extremely tight. West Virginia is a one-point road favorite over Virginia Tech. TCU is also a one-point road favorite at SMU.  Minnesota is an early 1.5-point favorite at Michigan State.

Clemson vs Wake Forest Early Odds & Pick

In a pivotal early-season showdown in the ACC, Wake Forest (3-0) hosts Clemson (3-0) at 12 p.m. ET Saturday and Clemson has opened as 8.5-point favorites. The Demon Deacons ended the Tigers’ five-year run as conference champions last season by winning the Atlantic Division.

Clemson won its ninth straight game Saturday, beating visiting Louisiana Tech 48-20 as Will Shipley had a career-high 139 yards rushing and two touchdowns. The Tigers are 3-0 for the seventh time in the last eight seasons and have won 35 consecutive home games.

Will Shipley turned on the jets on this TD 💨 @ClemsonFB pic.twitter.com/qroHH1IpKp

— ACC Network (@accnetwork) September 18, 2022

Clemson led just 13-6 at halftime. However, interceptions by Jeremiah Trotter Jr. and Malcolm Greene on consecutive possessions jump-started the Tigers in the second half.

Wake Forest survived a scare at home as it slipped past Liberty 37-36. The Demon Deacons held on when they stopped CJ Yarbrough on a two-point conversion attempt with 1:11 left.

Sealed the deal 🛑 pic.twitter.com/2v6grrtjAL

— Wake Forest Football (@WakeFB) September 18, 2022

Wake Forest rushed for just 21 yards on 26 attempts. Quarterback Sam Hartman, though, passed for 325 yards and three touchdowns.

While the Demon Deacons’ lack of success on the ground against a Group of Five defense is concerning, look for Hartman to keep Wake Forest in this game.

Pick: Wake Forest +8.5 (-110)

Florida vs Tennessee Early Odds & Prediction

Tennessee (3-0) hosts Florida (2-1) at 3:30 p.m. ET Saturday in a matchup of two ranked team in the SEC East. The Volunteers have opened as 7.5-point favorites.

Jalin Hyatt had five receptions for 166 yards and two touchdowns Saturday as Tennessee routed Akron 63-6 in Knoxville. Hyatt’s TDs covered 57 and 48 yards.

I think Jalin Hyatt is back y'all. pic.twitter.com/lVpPaGBPHT

— Karthik Venkataraman (@KarthikV_) September 18, 2022

Hendon Hooker passed for 298 yards, 251 of which came in the first half when the Volunteers built a 35-0 lead. Hooker’s Heisman odds have improved from +5500 to +4500 after a solid start to the season, which puts him among the top-ten favorites.

Trevor Etienne’s 3-yard touchdown run with five minutes remaining rallied Florida over South Florida 31-28 at home.

Etienne rushed for 56 yards on just eight carries while Anthony Richardson completed just 10 of 18 passes for 112 yards with two interceptions. The Gators survived a missed 48-yard field goal attempt by Spencer Shrader with 23 seconds left.

TREVOR ETIENNE GIVES FLORIDA THE LEAD 🐊 https://t.co/e2F1gwgyqb

— uSTADIUM uNIVERSITY (@uSTADIUMCollege) September 18, 2022

Since upsetting Utah in its opener, Florida has played two lackluster games in losing to Kentucky and barely beating USF. This is the Gators’ first time on the road this season and Tennessee and Neyland Stadium figure to be too much for them.

Pick: Tennessee -7.5 (-110)

That’s Outta Line

Tennessee is clearly better than a touchdown better than Florida and look for that line to go up over the course of the week.

Syracuse is a  nine-point favorite at home over Virginia on Friday night and that spread seems light.

The Orange are 3-0 with quality wins over Louisville and Purdue. While Virginia is 2-1, it lost by three touchdowns on the road to Illinois before returning home Saturday and edging Old Dominion 16-14 on a game-ending field goal.