"For me, basketball is over," he said.
Mutombo, an 18-year NBA veteran, appeared to get tangled with Portland center Greg Oden and came down hard on his left leg late in the first quarter of Game 2.
He stayed prone on the court under the Blazers' basket for several moments before he was taken away by stretcher. A preliminary examination revealed a knee strain and he was ruled out the rest of the game.
Afterward in Houston's locker room, the 7-foot-2 veteran was on crutches and fighting back tears.
"Nobody ever thought they'd be carrying the big guy out like a wounded soldier," he said.
The 42-year-old will be examined by doctors in Houston on Wednesday.
Mutombo is an eight-time All-Star who won the NBA's Defensive Player of the Year award four times and stands in second on the NBA's career blocks list with 3,289. He has played for Denver, Atlanta, Philadelphia, New Jersey, New York and Houston.
Mutombo played 18 minutes in Game 1 of the series and had nine rebounds. The Rockets won the opener, 108-81, before the Blazers evened the series with a 107-103 victory on Tuesday.
"I've had a wonderful 18 years of staying injury-free, so I just want to go out with my head up, no regrets," he said.