The Steelers will also not have safety Ryan Clark when they play the Broncos in their playoff opener this Sunday.
Mendenhall sustained an ACL injury on the final play in the first quarter of the 13-9 victory, and will miss the entire postseason.
While Mendenhall will miss the playoffs because of injury, Clark will not play in Denver because he has a sickle cell trait, and high altitude can lead to health problems.
Clark needed to have his spleen and gall bladder removed after playing in Denver in 2007, when he first learned of the trait. The Steelers will hold Clark out of Sunday's contest as a precautionary measure.
Ryan Mundy will start in Clark's place, while the Steelers signed Anthony Madison to take Mendenhall's roster spot.
The Steelers finished the regular season with a 12-4 mark and are the No. 5 seed in the AFC playoffs. They will face the AFC-West Champion Broncos at 4:30 p.m. (et) on Sunday.