He will miss about a month due to a moderate left ankle sprain.
The Spurs' other standout guard, Ginobili, has not played this season and isn't scheduled to be back from left ankle surgery until December.
"They're a tough team regardless," said Knicks guard Jamal Crawford, who led New York with 28 points.
"When they have Tim Duncan on the other side it's going to be tough, no matter who's out. He has a way of making everybody around him better."
San Antonio held New York to just 38 percent shooting and outrebounded the Knicks 60-48.
"Sometimes you're going to shoot well and sometimes you're not, but there's never a reason to play poor defense, and that's what was nice to see tonight," Spurs coach Gregg Popovich said.
Rookie George Hill started in place of Parker and scored a season-high 12 points.
"We wanted to test him," Crawford said. "But all he has to do is get the ball up the court and throw it in to Tim Duncan."
The Spurs (2-4) held a 67-64 lead entering the fourth quarter before they opened the period with 11 straight points as the Knicks missed their first four shots and did not score for the first 5 minutes. Zach Randolph's basket closed the deficit to 78-66, but New York could get no closer than nine the rest of the way.
Crawford's 28 came on 10-of-21 shooting, including 6 of 8 from 3-point territory. New York (4-3) had won three straight.
The odd start to the season continued for the Spurs. Not only were they without Parker and Ginobili, they opened the game with iron-man Bruce Bowen on the bench. It was the first time in 550 games that he played for the Spurs in which he was on the active roster and didn't start.
"They played hard, and they were desperate," Knicks coach Mike D'Antoni said. "They're a good team and give them credit, but we didn't play well. We need to shoot the ball better, move the ball a little better against a team like that."
Bowen checked into the game with 2:22 left in the first quarter.
He was replaced in the starting lineup at small forward by Ime Udoka, who got off to an 0-for-8 start from the floor.
Bowen finished with 13 points on 5-of-6 shooting. He ended the third quarter with a 3-pointer that broke a tie game and hit both of his shots while playing the entire fourth quarter.
"Coach (Popovich) says this is the way it is and that's that," Bowen said of not starting. "Coaches have a reason for doing those things. It's important for you to have trust in those things that they're trying to get accomplished.
"I'm happy. I enjoy playing the game. If Pop would let me, I would play 48 minutes."
The Knicks took their largest lead of the game when Crawford hit a 3-pointer to make it 46-40 55 seconds into the second half.
But the Spurs outscored New York 10-2 during the next 3:20 to go ahead 50-48. Hill hit a 3-pointer and made two free throws after that to give San Antonio a 52-48 advantage.
When Duncan made a turnaround bank shot from 11 feet, San Antonio was ahead 56-49 with 5:48 left in the third quarter.
Crawford made three of his next four shots - including a pair of 3-pointers - to tie the game with less than a minute to go in the third.
Bowen made a 3-pointer from the corner with less than a second, and the Spurs were ahead 67-64 heading into the fourth quarter.
The Knicks have a seven-game losing streak against the Spurs. New York is 1-10 overall against San Antonio since its last road win in the series on March 18, 2003. Notes: The Knicks are 0-3 when they score less than 100 points.
... New York was trying to win four straight for the first time since Jan. 8-13, 2006 ... Popovich has been remembered as a coach who had his tense moments when Parker was starting his career with the Spurs, but Popovich said he'd be more patient with Hill because he played shooting guard in college. "He's learning the (point guard) position at the same time he's running the team," the coach said. "More patience is definitely in order."
