New York (51-27) fell 118-111 in overtime at Chicago on Thursday. That ended the Knicks' longest win streak since they took 15 straight from March 1-April 2, 1994.
"It's over with," coach Mike Woodson said. "You can't win them all."
Carmelo Anthony scored exactly 36 for the third straight game for New York, which leads Central Division champion Indiana by two games with four left in the race for the Eastern Conference's No. 2 seed.
The Knicks have allowed some explosive performances by smaller perimeter players this season, most notably Golden State guard Stephen Curry's NBA season-high 54 points Feb. 27.
Former New York guard Nate Robinson scored a season-high 35 for the Bulls on Thursday, matching Toronto guard Alan Anderson's output March 22 as the most points scored by a reserve against the Knicks this season.
New York owns two close victories over Cleveland (24-54), with Anthony missing one contest with a sprained right ankle and only logging 14 minutes in the other as he left with a knee injury.
Irving scored a career-high 41 points in a 103-102 loss at New York on Dec. 15 that had Knicks point guard Raymond Felton marveling at the reigning Rookie of the Year's scoring prowess.
"When a guy gets that hot, there's nothing you can really do, other than just stay in front of him and make him take tough shots, which he did," Felton said after that win.
The Knicks limited Irving to 22 in a 102-97 road win March 4, ending their 10-game slide at Quicken Loans Arena. New York, however, was led in that contest by Amare Stoudemire's 22 points, and the forward is out for the remainder of the regular season.
Irving returned in that contest after missing three games with a hyperextended right knee. He also missed nine of 10 games between March 12-April 1, and is averaging 18.7 points but shooting only 33.7 percent in five since returning.
Irving scored 21 of his 27 points in the second half of Wednesday's 111-104 home loss to Detroit, and embattled coach Byron Scott has admitted that his star guard does not look the same.
"I don't think he's attacking as he normally does," Scott said. "You gotta ask him but I thought tonight he looked more tired in the first half that he did lately but in the second half, he picked it up."
Cleveland got good news Wednesday with the return of rookie Dion Waiters, who had 11 points in 15 minutes after missing 10 games with a knee injury. Scott said he plans on giving Waiters more minutes Friday.
The Knicks have a thin frontcourt with big men Tyson Chandler and Kenyon Martin sitting out Thursday. Chandler has a bulging disk and Martin a sprained left ankle.
Anthony picked up the slack on the glass with a season-high 19 rebounds against the Bulls. He's averaging 39.8 points in his last six games while J.R. Smith is scoring 24.9 over his last 11.
The Knicks haven't swept the Cavs since going 4-0 in 1993-94.