The headliner is No. 4 Ohio State at No. 9 Notre Dame, the season’s third top-10 showdown. The schools met in last year's opener with the Buckeyes winning a low-scoring affair. This will be only the sixth regular-season meeting between the geographic rivals.
Elsewhere, the Pac-12 farewell tour begins in earnest with three Top 25 matchups, including a big test for coach Deion Sanders’ 19th-ranked Colorado Buffaloes at No. 11 Oregon. Two-defending conference champion No. 10 Utah plays host to No. 25 UCLA. And the remaining two schools committed to the league - No. 15 Oregon State and No. 24 Washington State - face off in a game both programs will want to win to start conference play.
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The lineup also features a couple of recent playoff powers already with one loss hoping to stave off early elimination from College Football Playoff contention as No. 12 Alabama hosts No. 16 Ole Miss and No. 23 Clemson takes on third-ranked Florida State.
The rest of the Top 25 is in action as well, and there's some potential for upsets along the way.
Here’s how our staff sees the busy day unfolding.
This article originally appeared on USA TODAY: College football Week 4 picks, predictions for Top 25 schedule