Johnson, a possible MVP contender, caught a 66-yard, first-quarter touchdown pass from Vince Young and rushed for 117 yards on 28 carries with two other scores.
Young and Kerry Collins combined for 286 passing yards with one touchdown apiece.
Vincent Fuller scored on a 45-yard interception return, while the defense totaled five interceptions for the Titans (6-7), who have won six of seven since losing their first six contests.
St. Louis scored its only points on an 11-yard, fourth-quarter pass from Keith Null to Randy McMichael.
Null passed for 158 yards, but threw the five interceptions.
Keith Darby's lone carry was for 51 yards, and Steven Jackson rushed for just 47 yards on 19 carries for the Rams (1-12), who have lost their last five games.