It will be the third consecutive start for Kolb and the fourth game in a row in which he will see extensive action since Michael Vick suffered a rib injury during an Oct. 3 loss to the Washington Redskins.
Reid also said wide receiver DeSean Jackson will not play against the Titans after suffering a concussion when he absorbed a hit from Atlanta Falcons cornerback Dunta Robinson in last Sunday's 31-17 victory.
"There is some discomfort where (Jackson) took the blow on his right side, chest and neck," Reid said. "But he's sharp mentally."
The NFL fined Robinson $50,000 for the hit. Robinson said he would appeal the fine.
Kolb was the NFC Offensive Player of the Week following the victory over Atlanta, completing 23 of 29 passes for 326 yards and three touchdowns. He set career highs for completion percentage (79.3), passer rating (133.6) and TD passes, one a career-long 83-yarder to Jeremy Maclin.
Kolb started the season opener against the Green Bay Packers, but he suffered a concussion during the first half and was replaced by Vick, who started the next three games. Vick's injury forced Reid to go back to Kolb.
Reid had said Monday there was "a pretty good chance" Kolb would again start this weekend. Reid said it definitively Wednesday, adding that Vick would be in a backup role. Vick practiced Wednesday and has improved, although Reid said the quarterback is experiencing some soreness and is still limited.
"We'll give him a little bit more than we did last week," Reid said. "We kind of fed him a few plays on the scout team. We'll give him a little bit more and see how he feels."
Reid, when asked if there was anything Kolb could do this weekend to return to No. 1 on the depth chart, wouldn't say. But Kolb said he is taking it one week at a time and would "continue to prepare like a starter."
"That way," he said, "I'm ready when my name's called. Whatever (Reid) decides, he decides."
The Associated Press contributed to this report.