Penn State-Oregon headlines Week 5 predictions as college football picks against the spread

Week 5 of college football features a marquee non-conference showdown when No. 3 Penn State hosts No. 6 Oregon in Happy Valley, a prime-time environment that could resemble a national championship preview. The White Out atmosphere and a bye week for Penn State set the stage for a potentially pivotal performance from Drew Allar against Dante Moore, the Ducks’ quarterback who has shown flashes of dominance but also the kind of inconsistencies that make a road test feel decisive.

Across the rest of the week’s schedule, the New York Post’s Week 5 predictions lay out a slate with several marquee spreads. Penn State is listed at -3.5 against Oregon; Florida State sits at -6.5 versus Virginia; TCU is a +2.5 underdog at Arizona State; USC is favored by 6.5 points at Illinois; Syracuse is +5.5 at Duke; Wake Forest is +13.5 at Georgia Tech; Notre Dame is -4.5 over Arkansas; Utah State is +22.5 at Vanderbilt; Washington is +8.5 against Ohio State; LSU is +1.5 at Ole Miss; Texas A&M is -6.5 versus Auburn; Iowa is +7.5 at Indiana; Mississippi State is +7.5 against Tennessee; Arizona is +6.5 at Iowa State; and Georgia is -2.5 against Alabama. Best bets listed are TCU, Arizona and Georgia, with a season record noted as 26-34 (5-7) and an all-time mark of 1,392-1,309-31 from 2014-24.

Penn State’s Drew Allar has said the program needs to get over the hump against elite programs, and the Nittany Lions will lean on a raucous home crowd in the White Out to test Oregon’s Dante Moore. Moore has thrown five interceptions in three career road games against power-conference opponents and has yet to face a stadium as hostile as Happy Valley, making this a potential turning point in early-season narratives.

Beyond the headline matchup, the slate features a mix of traditional powers and rising teams as the season’s early narrative begins to take shape. Florida State, fresh off a dominant run that followed a marquee win over Alabama, travels to Virginia intent on maintaining its national title ambitions. TCU, seeking to prove it can contend for a Big 12 title and perhaps contend for Heisman consideration for quarterback Josh Hoover, brings a stout defense that excels on third-down; Arizona State represents a test that could keep TCU squarely in the mix. USC, riding a high-powered offense, faces Illinois as Jayden Maiava enters with one of the nation’s top passer ratings while USC also leans on a defense that leads the nation in sacks. Syracuse, dealing with the season-ending Achilles injury to quarterback Steve Angeli, hopes relief work from Rickie Collins can keep its momentum, while Duke hosts the Orange with expectations tempered by recent injuries and roster turnover.

Wake Forest’s visit to Georgia Tech presents a potential mismatch in tempo and playmaking, while Notre Dame aims to sustain its improvement against Arkansas, a game that could further define the Irish’s postseason outlook. Utah State’s trip to Vanderbilt offers a chance for a mid-major upset, and Washington’s road challenge at Ohio State tests the Huskies’ rapid ascent under a new offensive approach. The SEC slate features LSU at Ole Miss and Texas A&M hosting Auburn, with the Aggies’ progress under coach Brian Kelly and quarterback Marcel Reed attracting particular attention as they navigate a demanding schedule. Iowa travels to Indiana in a matchup that could hinge on field position and a stabilizing defense, while Mississippi State’s visit to Tennessee and Arizona’s trip to Iowa State add late-week intrigue. Finally, Georgia’s visit to Alabama stands as a potential antithesis of the sport’s typical power balance, a high-stakes matchup that reinforces the season’s escalating playoff chatter.

The breadth of this week’s games underscores the unpredictability that has become part of the sport’s appeal, especially as teams navigate travel, altitude, and crowd noise in environments designed to test focus and resilience. While the spread lines offer crisp betting anchors, the actual outcomes will reflect the evolving chemistry of rosters that have faced a rapid pace of change in recent seasons. The predictions listed above are compiled from the New York Post’s Week 5 coverage, which emphasizes marquee games and the spread-driven narratives that drive season-long discussions about elite programs, playoff positioning, and the ongoing evolution of college football.

In sum, Week 5 offers a blend of historic programs reasserting themselves on big stages and emerging teams seeking to redefine their trajectories. The Penn State-Oregon showdown anchors a day that could shape early-season sentiment about national-title contention, while the rest of the board provides a mix of clear favorites and potential upsets that will likely influence the postseason dialogue in the weeks ahead.