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College Football Week 6 Picks and Best Bets

Week 6 College Football Picks and Best Bets

College football Week 6 expert picks, predictions, and best bets are back as we gear up for an exciting slate of college football action in Week 6

As the college football season moves into Week 6, the stakes have never been higher. The dream of a playoff berth, especially in this inaugural 12-team College Football Playoff, is no longer a distant hope but a reality within reach. Every week, every game now feels heavier, the weight of expectation pressing down. One mistake could change a season; one moment could define a legacy.

Week by week, the script has been rewritten. Upsets have shattered the expected order, and breakout performances have carried teams beyond the limits of their preseason expectations. As conference play heats up, each game becomes a crucible—a proving ground where contenders and pretenders are separated. It’s no longer just about talent; it’s about resilience, the ability to rise in the moments that matter most.

And now, in Week 6, another opportunity arrives. For teams, it’s another step toward glory. For those searching for meaning in the chaos, it’s the time to look deeper. Where does the smart money lie in a season where nothing has been guaranteed? As the race tightens and the pressure mounts, Week 6 will ask the same question of everyone: Who truly belongs among the elite?

College Football Week 6 Picks and Best Bets

SMU vs. Louisville Betting Preview

All SMU vs. Louisville odds are from DraftKings Sportsbook and are correct as of Tuesday, Oct. 1.

  • Spread
    Louisville -7
  • Moneyline
    SMU +200 | Louisville -250
  • Over/Under
    57
  • Game Time
    Saturday, Oct. 5, Noon ET
  • Location
    L&N Federal Credit Union Stadium | Louisville, KY
  • How To Watch
    ESPN

Once riding the high of an undefeated season, Louisville returns home with a fresh sting— a 31-24 loss to Notre Dame. It was a game that slipped through their fingers, a game they could have won. With it, a piece of their College Football Playoff hopes faded. But for these Cardinals, the road is far from over. They come back to L&N Stadium with their eyes still locked on an ACC title, knowing that from here on out, every step counts.

On the other sideline, SMU arrives with confidence soaring. Their 42-16 rout of Florida State in their ACC debut sent a message, a declaration that they are ready for this new chapter. But now comes the true test—on the road, against a Louisville team desperate to right the ship.

It’s been decades since these two programs last met, and for the players on the field, this is all-new territory—new stakes, ambitions, and beginnings. Yet, while SMU’s offense, led by quarterback Kevin Jennings, has dazzled, the numbers tell a more complicated story. Turnovers have been their saving grace, masking games where both TCU and Florida State outgained them.

Louisville knows this. They’ve studied the film. Now, with a healthier Caullin Lacy back in the fold, Tyler Shough will look to attack through the air, while Ashton Gillotte and the Cardinals’ defensive front aim to disrupt the flow. The strategy is clear: stop Brashard Smith and put the pressure squarely on Jennings, still finding his footing in high-pressure moments.

For Louisville, this game is about more than just bouncing back—it’s about regaining their path. And in this one, the Cardinals find their way.

The Prediction: Louisville 31 – SMU 20

Best Bet: Louisville -7

Boston College vs. Virginia Betting Preview

All Boston College vs. Virginia odds are from DraftKings Sportsbook and are correct as of Tuesday, Oct. 1.

  • Spread
    Virginia -1
  • Moneyline
    Boston College +105 | Virginia -120
  • Over/Under
    53.5
  • Game Time
    Saturday, Oct. 5, Noon ET
  • Location
    Scott Stadium | Charlottesville, VA
  • How To Watch
    ACC Network

As the Virginia Cavaliers take the field against the Boston College Eagles in Week 6, both teams find themselves at a crossroads. Virginia, fresh off a bye week, enters as a narrow 1-point favorite—a line that’s shifted from its -3 opening—reflecting the cautious optimism around their 3-1 start. Boston College, now 4-1, narrowly escaped a scare against Western Kentucky without their starting quarterback, Thomas Castellanos. But with Castellanos back in the fold, the Eagles are eyeing another critical victory.

Virginia’s defense has been their anchor, allowing just 23.5 points per game and ranking 34th nationally. Against Coastal Carolina, they were stout against the run, holding their opponent to 82 rushing yards and 14 first downs. But their secondary showed vulnerability, surrendering over 300 yards through the air—an area of concern as Castellanos, who has thrown for 10 touchdowns this season, looks to take command of the Eagles’ offense.

Boston College’s defense has been equally formidable, giving up just 15.8 points per game, ranking 24th in the nation. Yet, last week’s performance against Western Kentucky exposed some cracks, as they allowed 355 total yards. Still, timely turnovers—two key interceptions—kept them in control.

Offensively, Castellanos will look to test Virginia’s secondary with the help of standout receiver Lewis Bond, who has tallied 279 yards and two touchdowns. Virginia’s best chance for success lies in their ground game, led by Treshaun Ward, who is averaging an impressive 6 yards per carry.

With Castellanos back, Boston College’s offensive firepower might be too much for Virginia to handle. The Eagles have the momentum—and the weapons—to leave Charlottesville with a victory.

The Prediction: Boston College 30 – Virginia 26

Best Bet: Boston College +1

Missouri vs. Texas A&M Betting Preview

All Missouri vs. Texas A&M odds are from DraftKings Sportsbook and are correct as of Tuesday, Oct. 1.

  • Spread
    Texas A&M -2
  • Moneyline
    Missouri +110 | Louisville -250
  • Over/Under
    48.5
  • Game Time
    Saturday, Oct. 5, Noon ET
  • Location
    Kyle Field | College Station, Texas
  • How To Watch
    ABC

Unbeaten and ranked No. 9 in the AP Top 25, the Missouri Tigers find themselves as underdogs heading into a critical road test. Texas A&M opened as a slight 1.5-point favorite, as Missouri prepares for a showdown at Kyle Field—looking to prove they belong among the nation’s elite.

Missouri’s perfect season hasn’t come without close calls. Against power-conference opponents, the Tigers have struggled to cover the spread, eking out a 27-21 win over 14.5-point underdog Boston College and a 30-27 overtime victory against Vanderbilt. Last weekend, their offense flashed promise, amassing 442 total yards and 22 first downs. But questions linger—especially on defense, where they allowed 324 yards and failed to force any turnovers.

Texas A&M, meanwhile, has covered the spread in both of their SEC matchups. The Aggies handled Florida 33-20 and squeezed by Arkansas 21-17 last weekend. Though their offense was held to just 297 yards, it was the defense that proved pivotal, forcing three takeaways and limiting Arkansas on third downs. Penalties also worked in A&M’s favor, with Arkansas committing ten infractions. The Aggies were fortunate to walk away with the win.

Despite A&M’s defensive strength, Missouri has the tools to pull off an upset. Brady Cook, paired with his top target, Luther Burden, can lead this Tigers team to a breakthrough moment on the road. In a game that feels balanced, Missouri has the chance to prove they’re more than just a surprise—they’re a contender.

This is the kind of stage where seasons are defined, and for Missouri, the opportunity is theirs to seize.

The Prediction: Missouri 27 – Texas A&M 24

Best Bet: Missouri +2

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