Lietzke shot a 3-under-par 69 to better Doug Tewell (67) by two shots at 9-under.
'I'm dedicating my first Senior Tour win to my mother's 89th birthday,' said Lietzke, who earned $262,500. 'She's been my No. 1 fan. Up until a couple of years ago, she would have walked all 18 holes when I played. I thought about her a lot today.'
Overnight co-leaders Hale Irwin and Jose Maria Canizares finished three shots back at 6-under following a pair of 74s. The two tied for third place with Gil Morgan (70) and Bruce Fleisher (71).
Lietzke, a 13-time PGA Tour winner, started the final round two strokes off the lead and birdied two of his first three holes.
The 50-year-old climbed to 9-under with a birdie at the par-5 6th, but dropped shots at both the 8th and 9th holes.
Lietzke righted the ship with a birdie at the par-4 11th, and then sealed the tournament with his final birdie at the par-4 14th.
This is the second week in a row that a player has won his maiden title on the Senior circuit. Bobby Wadkins won in his debut at last weeks Lightpath Long Island Classic.
Irwin got off to a horrendous start Sunday, playing his first four holes in 4-over. The tours all-time victory leader battled back to within two strokes of the lead, but a bogey at the 16th ended any chance he had for his third career 3M Championship victory.
Full-field scores from the 3M Championship