College Football Week 6 Picks: Best Bets (2026)

We’re in October now, meaning conference play is in full swing in the 2026 college football season. It’s been a year filled with chaos and some dominant programs, and in Week 6, there are a few massive games that will continue to shake up the AP Top 25 polls.

No. 7 Indiana vs. undefeated Nebraska gets Saturday’s slate off to a red-hot start. The Hoosiers are also undefeated as defending champions, and now, Cignetti’s crew heads into Lincoln to take on a souped-up Cornhuskers offense led by QB Anthony Colandrea.

Other big-time games in Week 6 include Oklahoma vs. No. 1 Texas, No. 21 UCLA vs. No. 13 Oregon, No. 10 LSU vs. Kentucky, No. 2 Georgia vs. No. 6 Alabama, and No. 19 USC vs. Penn State. The SEC and Big 10 are both on display within this week’s top-ranked matchups.

We’re coming off a profitable 2-1 result with my 3 Best College Football Bets for Week 5. After starting off 0-1 when Mississippi State QB Kamario Taylor failed to keep pace with the Crimson Tide, we cashed Under 45.5 between Ohio State vs. Iowa and Kentucky +3.0 during a thrilling overtime win over South Carolina.

Let’s run it back for even more profit with three of my best college football bets in Week 6. Follow me on X @Matt_MacKay for more college football betting analysis and free picks.

Get instant alerts when a line reaches your target via the BettingPros App >>

College Football Week 6 Picks: Best Bets

(Odds courtesy of DraftKings Sportsbook)

South Carolina vs. Florida (16)

Betting on Florida after they were dismantled 45-17 in their first loss of the season against Missouri just makes sense. The Gators return home to “The Swamp”, drawing a prime matchup against a South Carolina team that’s blown multiple leads and sits winless in SEC play.

Jadan Baugh is going to run roughshod over the Gamecocks in Week 6. Florida’s RB1 is the focal point of the offense, averaging 6.5 YPC and logging 11 rushing touchdowns.

South Carolina has allowed 4.0 YPC against 3 of 4 FBS opponents. The Gamecocks also have a terrible secondary, surrendering 12 passing touchdowns across their previous 3 contests.

Baugh and the Gators have put up 52+ points in all 3 games played at home this season. It’s only South Carolina’s second road game of the season, previously losing 49-18 to Alabama.

Let’s lay the points and take Florida -11.5 for our opening best bet on the Week 6 college football board.

Pick: Florida -11.5 (-108)

Georgia (2) vs. Alabama (6)

The marquee matchup in Week 6 is a prime-time tilt between undefeated Georgia and Alabama. The Crimson Tide have been putting up big numbers on offense, led by QB Keelon Russell, ranked second in the country, averaging 49.6 points per game.

QB Gunner Stockton has been equally impressive for the Bulldogs. The senior signal-caller has a 75 percent completion rate with 13 touchdowns and just 1 interception, while averaging 6.1 YPC.

Statistically, the Bulldogs’ defense is a top-20 unit, better than Alabama’s defense, sitting outside the top-50. However, the home-field advantage goes to the Crimson Tide, while it’s a good value spot, with 66 percent of public bets on Georgia’s moneyline.

Let’s back Russell to continue leading the nation’s second-ranked scoring offense to a 6-0 record with a massive win over Georgia.

Bet on Alabama’s moneyline at -122 odds.

Pick: Alabama Moneyline -122)

USC (19) vs. Penn State

Penn State finds itself in uncharted territory, starting its Big Ten play 0-2 in the Matt Campbell era. Now, the Nittany Lions host a high-flying USC offense in Week 6, after giving up 400 rushing yards to Northwestern.

Penn State’s offense hasn’t looked productive against conference opponents, scoring 27 points or less against Temple, Wisconsin, and Northwestern. Expect Campbell to lean into his defense, which ranks 25th in the nation, allowing just 16.o points per game.

USC was just contained by an equally stout Washington defense in Week 5, scoring 25 points and averaging under 3.5 YPC. Penn State has held opponents to a stingy 55 percent completion rate, giving up just 2 passing touchdowns all season.

Jayden Maiava has thrown for over 1,700 yards and 15 touchdowns. Most of the Trojans’ production has been through the air, which is where Penn State tends to excel.

We’re betting on Penn State’s mid-tier offense and top-20 defense to keep this game relatively low-scoring. We’re through a key number of 54.

Bet Under 54.5 at -108 odds between USC and Penn State for the final best bet on this Week 6 slate.

Pick: Under 54.5 (-108)