The franchise was able to successfully defend the National Football Conference (NFC) West division title and earned a playoff berth in the NFC Wild Card round against the Green Bay Packers, which they won in overtime by 51–45, the highest scoring game for two teams combined in a playoff game.

The following week on January 17, 2010, the Cardinals were blown out by the eventual Super Bowl champion New Orleans Saints 45–14 in the NFC divisional round.

The Cardinals would tie the game in the third quarter as quarterback Kurt Warner completed a 5-yard touchdown pass to wide receiver Larry Fitzgerald.

In the second quarter, trailing 10–3, the Jaguars lined up for another Scobee field goal only to have it blocked by backup defensive end Calais Campbell and returned by free safety Antrel Rolle for an 83-yard touchdown.

The Cardinals would extend their lead by halftime as quarterback Kurt Warner completed a 5-yard touchdown pass to running back Jason Wright.

Warner would find wide receiver Larry Fitzgerald in the third quarter for a 22-yard touchdown pass that increased the Cardinal lead to 28.

Afterwards, Houston would tie the game in the fourth quarter with quarterback Matt Schaub completing an 11-yard and a 17-yard touchdown pass to wide receiver Andre Johnson.

Coming off their home win over the Texans, the Cardinals flew to Qwest Field for a Week 6 NFC West duel with the Seattle Seahawks.

In the second quarter, the Cardinals would add onto their lead as kicker Neil Rackers made a 29-yard field goal.

In the second half, Arizona pulled away with Warner completing a 16-yard touchdown pass to wide receiver Steve Breaston in the third quarter and Rackers booting a 31-yard field goal in the fourth.

The Giants tried to come back in the fourth quarter as kicker Lawrence Tynes booted a 20-yard field goal, yet safety Antrel Rolle's final interception of the game sealed the deal for Arizona.

Coming off their impressive road win over the Giants, the Cardinals went home for a Week 8 duel with the Carolina Panthers in a rematch of last year's divisional game.

The Cardinals would respond as quarterback Kurt Warner completed a 14-yard touchdown pass to rookie running back LaRod Stephens-Howling.

Hoping to rebound from their home loss to the Panthers, the Cardinals flew to Soldier Field for a Week 9 duel with the Chicago Bears.

Arizona would deliver the opening strike in the first quarter as quarterback Kurt Warner completed an 11-yard touchdown pass to wide receiver Larry Fitzgerald.

Coming off their dominating road win over the Bears, the Cardinals went home for a Week 10 NFC West rematch with the Seattle Seahawks.

In the second quarter, Seattle would increase their lead as quarterback Matt Hasselbeck found tight end John Carlson on a 31-yard touchdown pass.

The Cardinals would get on the board with quarterback Kurt Warner's 28-yard touchdown pass to wide receiver Steve Breaston, but the Seahawks answered with kicker Olindo Mare getting a 32-yad field goal.

St. Louis attempted to rally; however, they were only able to muster a second Josh Brown field goal and a Steven Jackson touchdown.

With the win, the Cardinals improved to 7–3; however, Warner's status remained questionable for the next week's game against the Tennessee Titans.

With Kurt Warner on the sidelines due to injury, and in the tenth season since he won Super Bowl XXXIV over the Titans, the Cardinals fell to a game-winning rally led by quarterback Vince Young as he raced the Titans 99 yards down field over the final 2:37, converted two fourth downs, and fired the winning ten-yard touchdown on the final play to Kenny Britt.

The Cardinals' offense continued to flex its muscles as Warner found wide receiver Steve Breaston on a 17-yard touchdown pass.

Just then, Green Bay would tie the game again as Rodgers would complete an 11-yard touchdown pass to tight end Spencer Havner.

Arizona's defense would rise to the occasion in overtime as linebacker Karlos Dansby recovered a fumble and ran it back 17 yards for the game-winning touchdown.

Coming off their shootout win over the Packers, the Cardinals flew to the Louisiana Superdome for the NFC Divisional Round against the top-seeded New Orleans Saints.

The Saints would add onto their lead in the third quarter with a 43-yard field goal from kicker Garrett Hartley, followed by an 83-yard punt return for a touchdown by Bush.

Arizona tried to rally, but New Orleans' defense continued to shut down any possible comeback, effectively sealing a Cardinals blowout.