On October 16, 2006, during the sixth week of the National Football League (NFL) regular season, the Chicago Bears American football team defeated the Arizona Cardinals, 24–23, at University of Phoenix Stadium in Glendale, Arizona. The undefeated Bears staged the "comeback of the year" against the 1-win Cardinals after trailing by 20 points. This game is the first game in which the Bears won after trailing by 20 or more points since 1987 (they defeated the Tampa Bay Buccaneers, 27–26). According to the Elias Sports Bureau, it was the first win in Bears history in which they trailed by at least 20 points in the second half, and the Cardinals became the first team in NFL history to lose consecutive games in a season after being ahead by 14 or more points at the end of the first quarter in each of their games. The Bears also set an NFL record for the biggest comeback without scoring an offensive touchdown in league history. Cardinals quarterback Matt Leinart became the first quarterback in history to throw at least 2 touchdown passes in each of his first 2 career starts. The last time a team won after committing 6 turnovers was over 20 years prior.

The postgame press conference was notable for Cardinals head coach Dennis Green's profanity-laced rant, highlighted by the quote "The Bears are who we thought they were". The game was ranked #6 on NFL Top 10 on NFL Network for Top Ten Greatest Comebacks of All Time under the title "Cardinals Blow It"/"Monday Night Meltdown", as well as Top Ten Meltdowns at #7.

Before the meeting, the Bears lead the series 56–36, which also includes the Bears as the Decatur Staleys and Chicago Staleys, as well as the Cards as the Chicago Cardinals and St. Louis Cardinals (the team was also briefly known as the Phoenix Cardinals). Earlier in the year, in the preseason, the Cardinals defeated the Bears at Soldier Field 23–16 in a Friday night game.

The Bears were having a great season, being undefeated heading into the game at 5–0, having their best start to the season since 1989, having committed only 5 turnovers all season and averaging an NFL-best 31.2 points per game, and scoring 156 points compared to allowing only 36 points. This was the Bears' first Monday Night Football appearance since 2003. The Bears' 3rd year coach Lovie Smith was having the best season start of his coaching career, going 1–4 in 2004 and 2–3 in 2005 (despite making the playoffs in 2005), and notably defeated four of their first five opponents by more than 3 touchdowns (26–0 win against the Green Bay Packers, 34–7 win over the Detroit Lions, 37–6 win over Seattle, and 40–7 victory against Buffalo; their other game was a 19–16 win over the Vikings). The team was led by talented-yet inconsistent Rex Grossman, Thomas Jones, Muhsin Muhammad, linemen John Tait, Olin Kreutz, and Roberto Garza, defensive linemen Adewale Ogunleye, rookie Mark Anderson, who eventually recorded 12 sacks on the season, linebackers Brian Urlacher, Lance Briggs, and Brendon Ayanbadejo, rookie and future record holder for career returns for touchdowns and punt return touchdowns Devin Hester, a cornerbacking tandem in Charles Tillman and former record holder for the longest play in NFL history (broken by San Diego Chargers cornerback Antonio Cromartie) Nathan Vasher, Chris Harris, Mike Brown, and the 7th most accurate kicker in NFL history in Robbie Gould.

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