After three weeks of college football action, we’re beginning to seperate postseason hopefuls from the rest of the pack. However, there’s still plenty of time to turn this season on its head. With conference play having just begun across the country, we’ll see which potential powerhouses respond well to pressure. In a sport this volatile, Week 4 provides several intriguing underdogs itching for their chance to take down a favorite.
Let’s break down two plus money picks on DraftKings Sportsbook that could pull off an upset on Saturday.
Best CFB Upset Picks for Week 4
USC ML (+140) vs. Oregon
The Trojans have been stifled several times over the years by Oregon. However, this season’s Ducks appear vulnerable. A 37-31 loss to Oklahoma State is the primary reason for their middling #20 ranking. This group was also on upset alert during their season-opening, seven-point win at home vs. Boise State. In short, Dan Lanning’s crew has been sloppy at best for much of this season. An 84-0 shellacking of FCS Portland State last Saturday isn’t enough on its own to ignore the prior two games.
Oregon’s biggest issue has been the defense. Oklahoma State’s Drew Metsemaker managed to throw for 317 yards, while Boise State’s Maddux Madsen averaged over 12.0 yards per completion. The Ducks are also allowing 3.57 yards per rush attempt, tied for seventh-most among all Big Ten schools. On paper, USC has the exact kind of offense capable of exploiting those weaknesses. Under center, Jayden Maiava is a big-armed quarterback that leads all FBS players with 1,173 passing yards and 12 touchdowns. Just as impressive, he’s only handed out one interception this season. Granted, the team’s first four wins of the season haven’t come against elite competition. Still, those numbers can’t be ignored. On the ground, King Miller is one of the nation’s more underrated running backs. He’s gained 338 yards and three touchdowns on a conference-leading 64 rush attempts.
Allowing 35 points last weekend vs. Rutgers doesn’t inspire much confidence in this Trojans defense. Dante Moore and company present an even bigger challenge. However, all we’re asking for with this bet is a handful of timely stops. Something akin to the mediocre, but not disastrous, efforts from OKST and Boise State will be what USC should strive for. Typing that out, it doesn’t sound like a vote of confidence. However, Maiava and this offense are capable of winning a shootout. That’s especially true at home, where USC wields a stellar 21-5 record over the past three seasons.
Texas A&M ML (+285) at LSU
Not exactly the most promising moment to take a swing on Texas A&M. The team scored seven points during the first three quarters of its 31-21 defeat to Kentucky last week, looking downright awful on offense. With that being said, I’m willing to bet that Week 3’s disaster was an outlier. Keep in mind, the Aggies averaged 33.8 points per game in 2025. Returning stars Marcel Reed and Mario Craver form one of the nation’s top quarterback-wide receiver duos. On the ground, Rueben Owens is averaging over 62.0 rushing yards per game.
That alone doesn’t guarantee success against an also star-studded LSU squad. Quarterback Sam Leavitt is a true weapon, churning out 732 passing yards, 198 rushing yards and nine total touchdowns. However, he’s also handed out five interceptions in just three games. That level of recklessness with the ball is concerning, to say the least. LSU’s defense is solid, with edge rusher Princewill Umanmielen already notching six sacks. However, this group has had issues defending dual-threat quarterbacks. Look no further than A&M’s 49-25 domination during last season’s matchup between these schools. During that game, Reed scrambled for 108 yards and two touchdowns on the ground.
As more than eight-point underdogs, this isn’t the easiest trip to Baton Rouge for the Aggies. Still, the talent level between these two teams is closer than the current line suggests. It’s not as if A&M’s defense, allowing 281.3 yards per game, has slipped up this season. A timely turnover or two could be just what the Aggies need to deliver a massive upset on Saturday night.
