Despite their returns, the Knicks lost 105-100 to Portland.
Both Stoudemire and Anthony were considered questionable heading into Tuesday's game.
Stoudemire and Anthony went through a shootaround with the team around two hours before tipoff and it was determined Stoudemire's left knee was strong enough to allow him to suit up for the Knicks. Anthony's status was determined about 45 minutes before tipoff.
Stoudemire scored six points, grabbed one rebound and had two blocks in 16:41.
He played for the first time since undergoing a debridement on his left knee on Oct. 31.
Coming off the bench, Stoudemire was greeted by a standing ovation from fans at Madison Square Garden.
"I almost shed a tear when I walked out on the court with the standing ovation," Stoudemire said. "It was a phenomenal feeling. I haven't felt nothing quite like that before in my career."
Anthony scored 45 points on 14-for-24 shooting.
He poured in 11 of the Knicks' final 17 points, including a three-pointer with just under a minute to play to bring the Knicks to within three.
But he missed a three with 15 seconds to play that could have tied the game.
"I feel a little sore," Anthony said after the Knicks (21-10) lost for the third time in their last four games. "Just trying to get my legs back underneath of me, get the power and the strength back into my left leg. For the most part I was pretty good though."
New York got off to a 21-9 start with Stoudemire sidelined and some NBA observers and fans have wondered if the $100 million forward will impact the chemistry the Knicks have established.
Knicks coach Mike Woodson said Stoudemire would come off the bench initially and his playing time would be limited based on what the Knicks doctors advise.
"We've just got to gauge his minutes and work him slowly back in," Woodson said before tipoff on Tuesday. "I don't know if I'll put him in the first quarter of the second quarter, but we'll figure it out as the game goes along."
Stoudemire felt improvement in his knee after participating in scrimmages on Sunday and Monday but admitted that his knee is not fully healthy. After the game he said he didn't feel much pain in his knee.
He plans to practice with the Knicks on Wednesday.
Prior to tipoff, Stoudemire said he wanted to return on Tuesday, in part, to help ensure that some of his injured teammates have ample time to rest.
Rasheed Wallace missed his ninth straight game due to a stress reaction in his left foot. The Knicks are also without starting point guard Raymond Felton, who sprained his right pinkie finger and is out for at least a month. Guard Iman Shumpert has been out for the entire season recovering from offseason ACL surgery.
"I want to make sure that those guys' bodies hold up for the duration of the season," Stoudemire said.
The 10-year veteran understands the team's plan to limit his minutes.
"We don't want to overdo it right now," he said. "(We) want to still take precautionary measures as I continue to improve."
Stoudemire is also confident that his knee can withstand the rigors of an NBA schedule.
"The coaching staff and the training staff have a plan for me to make sure that I'm a 100 percent and ready to go, especially going into the later half of the season," he said. "That's the bigger picture."