Irving's output marked a career-high and also set a new high for the NBA this season.
The 6-foot-3 guard connected on 17 of his 36 shot attempts, including 11 of 19 from beyond the arc, and also added five assists, four rebounds and two steals in 39 minutes.
James did not play in the game after spraining his wrist during Cleveland's win at Detroit on Tuesday.
"Yo man, when I tell you I probably just witnessed one of the greatest single performances, live, in my life, man – that’s exactly what I just saw," James said of Irving's effort in a Bleacher Report video. "That boy Kyrie, he already stamped his All-Star nod, but he even … three more stamps tonight, man. Fifty-five in a win, game-winning three. You know, he carried us all night man. Big shot after big shot after big shot.
"Kyrie, the truth, you the truth, kid. Keep going man, that was huge. That’s what it’s all about, man, in this league, baby. Support, and great performances and brotherhood, man. And that boy did it tonight, man. Kyrie, all star, superstar on his way, leader on his way. Everything, man, keep going."
Cleveland has won eight consecutive games and currently trails the Chicago Bulls by three games for the No. 4 seed in the Eastern Conference.