[9] Levi's Stadium in Santa Clara, California, was announced as the host site for the fifth College Football Playoff National Championship on November 4, 2015.

[12] Clemson defeated the Notre Dame Fighting Irish in the Cotton Bowl Classic on December 29 to advance to the championship game.

[14] On January 3, it was confirmed that three Clemson players, including starting defensive lineman Dexter Lawrence, would remain suspended from playing by the NCAA, due to drug testing in advance of the Cotton Bowl Classic that showed "trace amounts of a banned substance", which was identified as ostarine.

However, three plays later, the scoring was opened by Clemson cornerback A. J. Terrell, who intercepted a Tua Tagovailoa pass and returned it 44 yards for a touchdown.

On their ensuing drive, Clemson continued the offensive trend of the first quarter with a 62-yard pass of their own, from Trevor Lawrence to Tee Higgins, which set up a 17-yard touchdown rush by Travis Etienne on the next play.

Now trailing 14–7, Alabama marched downfield on their next drive, covering 75 yards in ten plays, to score a touchdown with an opportunity to tie the game.

Clemson would soon recapture the lead, as Lawrence led the Tigers' offense down the field in six plays; the drive was capped by a one-yard touchdown rush by Travis Etienne.

Alabama's next drive spanned 59 yards before they failed to convert a 4th-and-4 on Clemson's 14-yard-line, giving the Tigers the ball with just under six minutes to play in the third quarter.

Alabama began their fourth second-half drive with just over eleven minutes on the clock and Jalen Hurts at quarterback; it ended in a three-and-out, and Mike Bernier's punt was downed at the Clemson one-yard-line.

After draining more than seven minutes on the clock and with the ball on Alabama's 17-yard-line, the majority of Clemson's offensive starters were removed from the game, and Chase Brice was put in at quarterback.

As in 2018, the network also promoted an off-site concert that was televised at halftime during ESPN's broadcast, featuring rock band Imagine Dragons, including a "special collaboration" with rapper Lil Wayne,[30] on Treasure Island.