The opening weekend provides two matchups in which both teams appear in at least one of the AP, Coaches or SP+ top 25s. Louisville–Ole Miss is the weekend’s only AP-ranked matchup, while Clemson–LSU qualifies because Clemson is No. 23 in both the Coaches Poll and SP+ despite narrowly missing the AP Top 25.

Rankings at a Glance

Matchup	AP	Coaches	SP+
Clemson at LSU	Clemson NR, LSU 11	Clemson 23, LSU 13	Clemson 23, LSU 10
Louisville vs. Ole Miss	Louisville 24, Ole Miss 9	Louisville NR, Ole Miss 10	Louisville 27, Ole Miss 16

No. 23 Coaches/SP+ Clemson at No. 11 AP LSU

Saturday, Sept. 5 — 6:30 p.m. CT — ABC
Tiger Stadium, Baton Rouge, Louisiana
Line: LSU -10; Total: 50.5 at BetMGM on Wednesday morning

Lane Kiffin’s LSU debut comes against the same opponent LSU defeated 17-10 in last season’s opener. Both programs subsequently stumbled to 7-6 finishes, but LSU responded by hiring Kiffin and assembling the nation’s top-rated transfer class. The additions include former Arizona State quarterback Sam Leavitt, edge rusher Princewill Umanmielen and offensive tackle Jordan Seaton.

Leavitt gives Kiffin an experienced dual-threat quarterback who went 16-4 in 20 starts at Arizona State. His most imposing target may be 6-foot-7 tight end Trey’Dez Green, who led LSU with seven receiving touchdowns last season and already owns the program’s career record for touchdown catches by a tight end. Seaton should upgrade an offensive line that was LSU’s most obvious weakness in 2025, although one elite tackle cannot immediately solve every protection problem.

Clemson will counter with Christopher Vizzina at quarterback. The fourth-year junior owns only one previous start, but it was an encouraging one: 317 yards and three touchdowns against SMU. Freshman Tait Reynolds is also expected to play, creating an additional preparation problem for LSU. Vizzina has useful pieces around him in running back Gideon Davidson and receiver T.J. Moore, but Clemson lost seven offensive starters, including Cade Klubnik, its top two receivers and three linemen.

The stronger Clemson argument lies on defense. Linebacker Sammy Brown recorded 107 tackles last season, while defensive end Will Heldt supplied 15.5 tackles for loss and 7.5 sacks. Cornerback Ashton Hampton gives the secondary a proven matchup option. Still, that unit also lost seven starters, including Peter Woods, T.J. Parker and Avieon Terrell.

The ten-point spread reflects more than poll position. LSU has the more experienced quarterback, a major home-field advantage and an offensive coach skilled at isolating new defenders. Clemson’s best route to an upset is to pressure Leavitt without surrendering explosive plays, establish Davidson early and keep Vizzina out of predictable passing situations. If LSU’s rebuilt line holds up, Green’s size and Leavitt’s mobility should eventually create too many problems.

What decides it: Clemson’s ability to protect its inexperienced quarterbacks in a night game at Tiger Stadium.

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No. 24 AP Louisville vs. No. 9 AP Ole Miss

Sunday, Sept. 6 — 6:30 p.m. CT — ABC
Nissan Stadium, Nashville, Tennessee
Line: Ole Miss -7; Total: 55.5 consensus on Wednesday morning

Ole Miss begins the Pete Golding era with considerably more continuity than the coaching change suggests. Golding guided the Rebels through last season’s College Football Playoff after Kiffin left for LSU, helping them beat Tulane and Georgia before losing to Miami in the semifinal. Ole Miss finished 13-2, setting a school record for victories.

The Rebels return one of the country’s most dangerous backfields. Trinidad Chambliss passed for 3,937 yards with 22 touchdowns and only three interceptions last season while adding 527 yards and eight scores on the ground. Kewan Lacy carried 307 times for 1,567 yards and an FBS-leading 24 rushing touchdowns. The concern is tackle: Ole Miss lost both starters to the NFL, and Louisville owns the edge personnel to test their replacements.

Clev Lubin leads that Cardinals pass rush after recording 8.5 sacks last season. Louisville also finished first in the ACC in pass defense, giving Jeff Brohm a group capable of forcing Ole Miss to sustain drives instead of living on explosive plays. The matchup becomes more difficult when Chambliss escapes containment, however. Louisville must account for him without opening cutback lanes for Lacy.

Offensively, the Cardinals are turning to Ohio State transfer Lincoln Kienholz. His experience is limited, but Brohm has a strong history of developing quarterbacks and designing early completions that settle a new starter. Running back Isaac Brown should be the foundation. Golding called Brown one of the best backs Ole Miss will face this season after he averaged 8.8 yards per carry in 2025.

Louisville’s greatest concern is an offensive line returning only one experienced starter. That is a dangerous weakness against an Ole Miss defensive front that expects to rotate fresh pass rushers throughout the game. If the Cardinals fall behind the chains and force Kienholz to throw against Golding’s disguised pressures, the Rebels can take control quickly.

Louisville has enough defensive talent and backfield explosiveness to make the touchdown spread uncomfortable. The upset path involves Brown controlling the pace, Kienholz avoiding turnovers and Lubin disrupting Ole Miss’ new tackles. Over four quarters, however, the Chambliss-Lacy combination gives Ole Miss the safest and most proven answer in the game.

What decides it: Whether Louisville’s rebuilt offensive line can keep Kienholz comfortable against Ole Miss’ pressure packages.