Mendenhall hinted at as much in a Feb. 25 column he wrote for the Huffington Post when he said, "As I write this, today is the day that the journey is over and I am fully at peace. Eagerly looking to a new way, which lies ahead."
Agent Mike McCartney confirmed via Twitter on Sunday that Mendenhall had decided to end his playing career.
The 26-year-old Mendenhall was drafted by the Pittsburgh Steelers in the first round of the 2008 draft. In six NFL seasons, Mendenhall rushed for 4,236 yards and scored 39 total touchdowns.
He was reunited last season with Cardinals coach Bruce Arians, his offensive coordinator in Pittsburgh from 2008-2011.
The sixth-year back battled turf toe for a majority of last season. Once healthy in 2013, Mendenhall scored five touchdowns in his final eight games but never eclipsed the 100-yard mark in a game. Only four other running backs had more touchdowns than Mendenhall during that stretch.
After last season ended, Mendenhall told Arians he wanted to write books and do different things than play football. And so, after rushing for 687 yards on 217 carries (both team highs) and scoring eight touchdowns last season, Mendenhall now believes he has played his last NFL down.
Information from ESPN.com Cardinals reporter Josh Weinfuss and The Associated Press was used in this report.