Irving injured his quad during Monday's win in Denver. He was originally listed as probable before being ruled out on Wednesday.
Celtics coach Brad Stevens said Irving was "pretty stiff" on Wednesday morning. The team plans to re-evaluate Irving before Thursday's off-day practice. Stevens deemed him day-to-day.
Third-year guard Terry Rozier will start his first game in place of Irving.
Stevens was asked how he delivered the news.
"I said, 'Terry you're starting,'" Stevens deadpanned. "I mean, that's what I said. He's started a couple of exhibition games. Terry's been great for us all year."
"I don't think [starting] changes what we need [Rozier] to do, what he does," Stevens added. "He'll probably play more minutes, which everybody loves. But I feel really good about Terry Rozier out there. I think he's had a great year. He's shown consistent progress since he's been here. And it's a great opportunity for him tonight."
This is the fourth game Irving has missed this season, after having sat out single games for a facial fracture, shoulder soreness and a left quad contusion. The Celtics are 1-2 without him this season.
Boston already is playing without top reserve guard Marcus Smart, who is set to miss two weeks after lacerating his right hand in a non-basketball injury last week. Shane Larkin, who was held out versus the Nuggets, is listed as questionable against the Knicks due to right knee soreness.
Rozier had been questionable to play in Denver due to a sprained ankle, but he toughed out 30 minutes with Boston short-handed.
The Celtics also listed rookie big man Guerschon Yabusele as probable with a sprained ankle that forced him to miss the team's West Coast trip.
Boston had called up two-way player Kadeem Allen to add depth given its rash of injuries.
Irving, voted an All-Star Game starter, is averaging 24.9 points, 5 assists and 3.7 rebounds over 33 minutes per game in 48 appearances for Boston this season.
The Celtics sit atop the Eastern Conference but are clinging to a one-game lead over the Toronto Raptors.