Joe Flacco completed 12 of 23 passes for 282 yards and two touchdowns for the Ravens, who limped into the AFC wild-card playoff game with losses in four of their last five regular season games.
Flacco, who becomes the first quarterback to earn at least one playoff win in each of his first five years, averaged more than 12 yards in each of his completions.
His favorite target was Anquan Boldin, who caught five passes for 145 yards, including an 18-yard scoring strike from Flacco in the fourth quarter that gave the Ravens their 24-9 lead.
Rookie Andrew Luck, who guided the Colts' march to the postseason following last year's miserable 2-14 campaign, threw for 288 yards on 28 of 54 passing but was victimized by too many drops by his receivers.
Indianapolis, despite driving downfield repeatedly, had to settle for three field goals by veteran Adam Vinatieri.
The 37-year-old Lewis, a 13-time Pro Bowler widely considered the best linebacker of his generation, announced Wednesday he would be retiring after this season, his 17th in the National Football League.
Lewis, a 13-time Pro Bowl selection and former Super Bowl MVP, missed the last 10 games with a torn right triceps. He started the game and made 13 tackles, each of them cheered wildly by the crowd of 71,379 at M&T Bank Stadium.
The Ravens travel to Denver next Saturday, meaning the victory over the Colts was Lewis's last before his home fans.
Baltimore took control of the game in the third quarter when Flacco found Dennis Pitta on a 20-yard touchdown pass to give the Ravens a 17-6 lead.
A 26-yard field goal by Vinatieri in the final minute of the quarter trimmed the Ravens' lead to 17-9 but the Colts were able to get no closer.