Arizona limped to a 3-13 mark under the watch of Wilks, who was hired on Jan. 22 to replace the retiring Bruce Arians. The record was the worst in 18 years for the Cardinals, who secured the top overall pick of the 2019 NFL Draft.
Wilks was in the midst of his first head-coaching job after serving as a defensive coordinator.
The 49-year-old Wilks became the first one-and-done head coach since Chip Kelly was fired by the San Francisco 49ers in 2016 and the first by the Cardinals since Joe Kuharich was relieved of his duties following a 4-8 season in 1952.
"Any time something happens like that, you feel bad for a person," defensive end Markus Golden said. "At the same time, he came in and went hard every day, so I respect him. I know he gave it his all. I know he can walk away with pride and say, 'Hey, at least I came in hard every day and tried to do my job and tried to help this team win.' So I respect coach Wilks. He brought his all every day."
Arizona dropped its first four games of the season before securing its first two wins against the same foe: the 49ers. The Cardinals also defeated the Green Bay Packers on Dec. 2.
Under Wilks, Arizona owned the league's worst offense, ranking last in average points per game (14.1), total yards (241.6), passing yards (157.7) and rushing yards (83.9).
Wilks fired offensive coordinator Mike McCoy midway through the season, but the troubles continued.
The Cardinals' rush defense went from yielding 89.6 yards per game and 12 touchdowns in 2017 to 154.9 yards per contest and 25 scores in 2018.
Arizona's decision to part ways with Wilks came after wide receiver Larry Fitzgerald publicly came out in defense of the coach.
Fitzgerald showed his support of Wilks via a text to NFL Network's Ian Rapoport last week.
"We all would want him back," Fitzgerald wrote.
He didn't stop there.
"I love Wilks," Fitzgerald said. "Great dude. We all play hard for him. That's the team -- not me alone -- speaking on it."