College football picks and predictions for all 58 games in Week 6, straight-up and ATS

The Week 5 college football schedule was a bit light on marquee matchups, and we hope you took that opportunity to hydrate and reconnect with some loved ones. Because the Week 6 slate is loaded with intrigue, from the game of the year so far in Georgia-Alabama to a Red River anxiety bowl, several other SEC College Football Playoff hopefuls making tricky road trips and a downright fascinating slate in the Big Ten.

We've continued to roll with our college football picks and predictions this season, and we're not stopping. These are our picks for every Week 6 game with predictions both straight-up and against the spread across all 58 games.

2026 College Football picks record — Straight-up: 311-67 (Last Week: 41-17) | Against the spread: 202-175 (Last Week: 33-25)

College football picks for every Week 6 game, straight-up and ATS

Getting into October means the dawn of early-week college football, and we got our week started off right thanks to Troy putting the hammer down on a flailing Southern Miss team on Tuesday. We've got a matchup with big-time American implications between USF and UTSA on Thursday, and Friday brings us several intriguing power-conference games like suddenly surging Florida State at Louisville, Iowa at Washington and Iowa State at BYU. Hopefully we can keep the good vibes rolling after another strong performance in Week 5.

Expert picks and analysis for the biggest Week 6 CFB games

Texas (-7.5) at Oklahoma

This is a big number for a game between two arch rivals and blue bloods, and there's always a chance that Oklahoma's defense mucks things up enough to keep it close into the fourth quarter. Then again ... I mean, have you seen the Sooners try to move the ball lately? John Mateer is a disaster waiting to happen, both miserably inefficient and also proven to crippling sacks and interceptions.

The Horns have one of the best defenses in the country, one that should have no problem bottling up the Oklahoma offense. If Arch Manning just keeps things on the rails and doesn't beat himself, I don't foresee Texas having trouble here, even if Red River is good for a curveball every now and then.

Indiana at Nebraska (+7.5)

I feel a bit like Charlie Brown kicking the football here; how many times have the Huskers started strong only to flop in a big spot at home? And yet, I haven't been all that impressed by the way that Indiana has started this season, with sleepwalks over cupcakes and a too-close-for-comfort win against Northwestern to date. Their only road game so far has been at Rutgers, which hardly feels like it counts (and I say this as a New Jersey native).

The Huskers have an explosive offense with Anthony Colandrea at the controls, and star RB Jamal Rule should be healthier after missing last week's romp over Maryland. Do we really trust that Josh Hoover has kicked his turnover habit for good? At over a TD, I'm willing to find out.

UCLA (+11.5) at Oregon

This is less a fade of Oregon — even with Dylan Raiola filling in once again for Dante Moore — and more a reflection of how strong UCLA has looked so far this season, enough that I think they can at least keep this game competitive. Bob Chesney's team is fast, physical and owns one of the most dynamic rushing games in the country; really, all they need Nico Iamaleava to do is keep things on schedule and stay out of the way.

Can he do that in a hostile environment in Autzen? I'm a believer in what Chesney's building, and it's worth remembering that this Oregon defense has looked vulnerable against Oklahoma State, Boise State and USC. The Ducks should win, but this feels like a disrespectful number.

USC at Penn State (-1.5)

On paper, this wouldn't seem to make all that much sense, considering how mediocre Penn State has looked against real competition in year one under Matt Campbell. But I'll believe that a Lincoln Riley team can cross into the Eastern time zone and win a big game — or heck, any game — when it actually happens, and no sooner.

This is a Whiteout spot in Happy Valley, and you know the Nittany Lions are going to come out desperate. Can the Trojans match that energy? Can this defense actually play with consistency for once? Maybe they'll prove me wrong, but they haven't exactly earned the benefit of the doubt.

Georgia (+1.5) at Alabama

A lot of this comes down to factors out of either team's control. The weather in Tuscaloosa on Saturday night is expected to be brutal, thanks to a major storm that's set to sweep directly through the area. There's even talk that the game might be postponed, and obviously the most important thing is that everyone stays safe.

Even if we are able to safely play football, it's going to be a true slopfest — and I can't help but feel like that favors Kirby Smart and the Dawgs. Alabama's defense and running game have passed the test so far this season, but I simply trust Georgia a little more in the trenches, and I trust Gunner Stockton to make the right decisions and protect the ball a little more than Keelon Russell given the experience gap between the two. In a true toss-up, that's enough to make the difference.

Note: All odds are courtesy of FanDuel Sportsbook. Odds change periodically and are subject to change. If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.

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