Despite a loss to the Indianapolis Colts in Week 16, the Cardinals clinched a playoff berth for the first time since 2015 after the Minnesota Vikings lost to the Los Angeles Rams.

Green prior to the season starting, the team suffered their second consecutive late-season collapse, only winning four out of their last ten games, resulting in them losing their lead in the division and dropping to the fifth seed.

In the Wild Card of the playoffs, the Cardinals fell to the rival Los Angeles Rams on their way to win Super Bowl LVI.

Also, with the Broncos, the Raiders, and the Panthers losing their first games of the season, the Cardinals became the last undefeated team in the NFL.

This was the first game where former Texans DeAndre Hopkins and JJ Watt played against their former team, as well as tight end Zach Ertz's debut with the Cardinals.

The Packers handed the Cardinals their first loss to deny them a perfect season with a 24–21 victory on Thursday Night Football, despite entering the game without their top three wide receivers—Allen Lazard and All-Pro WR Davante Adams missed the game due to COVID protocols, while Marquez Valdes-Scantling was still recovering from a groin injury suffered in Week 3.

Green was picked off in the endzone by Packers cornerback Rasul Douglas, who began the season on the Cardinals practice squad.

Despite Kyler Murray and DeAndre Hopkins not playing, the Cardinals dominated the game to sweep the season series for the first time since 2018.

Kyler Murray and DeAndre Hopkins returned to the field after the bye and connected for a 21-yard touchdown in the first quarter.

With the loss, the Cardinals finished the season 11–6, earning a Wildcard spot in the 2021–22 NFL playoffs as the 5th seed.