Arizona promoted quarterbacks coach Byron Leftwich to the role in a corresponding move. The Cardinals announced McCoy's departure on Friday.
The decision follows the Cardinals' 45-10 loss to the Denver Broncos on Thursday. Arizona is now 1-6 on the season. McCoy, 46, entered the NFL as the Carolina Panthers' quarterbacks coach in 2000. He also served as a wide receivers coach and passing game coordinator with the Cardinals until becoming the Denver Broncos' offensive coordinator in 2009.
McCoy held that role until being hired in 2013 as the head coach of the San Diego Chargers. He was the Broncos' offensive coordinator again in 2017, but was fired midseason.
The Cardinals rank last in yards per game and are averaging the second-fewest points per game.
Leftwich joined the franchise as a coaching intern in 2016 and stayed on as the team's quarterbacks coach in January of 2017.
"Everybody is going to be evaluated across the board," Cardinals coach Steve Wilks told reporters Thursday. "As I said before, we've gotta find ways to get this thing moving in the right direction. Not acceptable and our fans deserve better."
The Cardinals host the San Francisco 49ers at 4:25 p.m. on Oct. 28 at State Farm Stadium in Glendale, Ariz.