After six successive wins to start their title defence, the Cavs were halted 110-106 by the Atlanta Hawks on Tuesday.
Marc Gasol tapped in on the buzzer to lift the Memphis Grizzlies to a 108-107 victory over the Denver Nuggets.
The Portland Trail Blazers and the Brooklyn Nets were also victorious.
The Cavaliers had no answer for Dennis Schroder, Kent Bazemore and Paul Millsap.
Schroder was 10-of-16 from the field for 28 points, Bazemore posed 25 of his own, while Millsap contributed 21 of his own.
Dwight Howard also collected 17 rebounds for the Hawks.
The Cavs were led by Kyrie Irving (29 points), Kevin Love (24 points, 12 rebounds) and LeBron James (23 points).
Gasol tipped in Vince Carter’s inbound pass to give the Grizzlies a late win in Memphis.
There were 0.7 seconds remaining when Carter inbounded the ball.
Gasol finished with 19 points as the Grizzlies ended a run of back-to-back defeats.
Damian Lillard and C.J. McCollum combined for 71 points to lead the Trail Blazers past the Phoenix Suns 124-121.
The Nets outlasted the Minnesota Timberwolves 119-110.
Elsewhere, the Los Angeles Lakers lost 109-97 to the Dallas Mavericks and the New Orleans Pelicans were beaten by the Sacramento Kings 102-94.
The Golden State Warriors will face the Mavericks on Wednesday. The San Antonio Spurs meet the Houston Rockets, while the Los Angeles Clippers take to the court against the Trail Blazers.