The loss ended the Colts' turnaround season in which they went from 2-14 to the playoffs in coach Chuck Pagano's first year in Indianapolis (11-6).
Pagano missed 12 weeks while undergoing treatment for leukemia and returned last week.
Offensive coordinator Bruce Arians, who went 9-3 as interim coach, was absent Sunday after being hospitalized with an undisclosed illness.
Quarterback coach Clyde Christensen called the plays, but Baltimore's suddenly revitalized defense - inspired by Lewis' pending retirement, no doubt - never let standout rookie QB Andrew Luck get comfortable.
Indy's only points came on three field goals by Adam Vinatieri, from 47, 52 and 26 yards.
Luck completed 28 of 54 passes for 288 yards. It was the most attempts by a rookie in a playoff game.
Reggie Wayne had 108 yards on eight receptions and moved into second in career playoff catches with 91 - 60 behind leader Jerry Rice. But the Colts, who moved from Baltimore to Indianapolis in 1984 - they still are despised here - became the second NFL team to improve to 11 wins following a two-win season and then lose in the opening round of the playoffs.
The Ravens also beat the 2008 Dolphins in a similar scenario.
Both teams were sloppy early on, with Rice losing a fumble, Lewis dropping a potential interception, and Luck being stripped of the ball on a sack.
But Rice atoned with a 47-yard gain on a screen pass, leading to Vonta Leach's 2-yard touchdown.
That Pro Bowl backfield was bolstered by the kick returns of another Pro Bowl player, Jacoby Jones. He gained 60 yards on kickoff runbacks and 57 on punt returns.
Vinatieri, familiar with big kicks in the playoffs after winning two Super Bowls for New England with field goals, made a 47-yarder in the second quarter, a 52-yarder as the first half expired, and a 26-yarder near the end of the third period. But he also missed a 40-yarder wide right.