The move came hours after the Cardinals were bludgeoned at home 45-10 by the Denver Broncos on Thursday night to fall to 1-6 on the season.
First-year head coach Steve Wilks told reporters after the loss that it was “premature” to talk about making any changes, but another listless offensive performance prompted the move to dismiss McCoy.
Cardinals quarterbacks coach Byron Leftwich will replace McCoy, according to the team. Leftwich also will call plays, the Arizona Republic reported, citing a source.
McCoy, who was fired by the Broncos during last season following a six-game losing streak, watched his former team limit Arizona to 223 yards of total offense.
Rookie quarterback Josh Rosen was sacked six times and committed five turnovers against Denver, which returned a pair of interceptions for touchdowns in bolting to a 21-3 first-quarter lead.
The Cardinals entered Thursday night’s matchup ranked last in total offense, last in rushing offense, last in total first downs and last in third-down conversion percentage.
McCoy was head coach of the then-San Diego Chargers from 2013-16, compiling a 27-37 record. He guided the franchise to identical 9-7 marks in his first two seasons but the Chargers went 4-12 and 5-11 in his last two, leading to his firing.
Wilks, who replaced the retired Bruce Arians during the offseason after serving as the defensive coordinator with the Carolina Panthers, also had been asked about McCoy’s job status following Sunday’s 27-17 loss at Minnesota.
“I would say all our jobs are in jeopardy, including mine if we don’t win,” Wilks responded.
Arizona signed a pair of veteran quarterbacks during free agency, bringing in former No. 1 overall pick Sam Bradford and Mike Glennon. The Cardinals also traded up five spots in the draft to take Rosen at No. 10 overall.
Rosen supplanted Bradford as the starter in Week 4 but has thrown for only 820 yards with three touchdowns and five interceptions in four-plus games.
Star wide receiver Larry Fitzgerald has been hobbled by a hamstring injury and has only 26 receptions for 298 yards and one touchdown.
Running back David Johnson also has been ineffective, failing to surpass 55 yards rushing in six of the seven contests and managing only 39 yards on 14 carries in Thursday’s defeat.
Johnson, who suffered a season-ending wrist injury in Week 1 last year, rushed for 1,239 yards and 16 touchdowns in 2016.
Leftwich, a former first-round draft pick of the Jacksonville Jaguars, played nine seasons in the NFL. He also spent time with the Pittsburgh Steelers and Tampa Bay Buccaneers.
The Cardinals hired Leftwich as a coaching intern in 2016 and named him the team’s quarterbacks coach in January 2017.