Memphis - third in the Western Conference boasting a 21-6 win-loss record - were no match for the Cavaliers with power forward Zach Randolph sidelined due to a sore and swollen right knee.
The Cavaliers (16-10) made the most of Randolph's absence, claiming back-to-back wins at Quicken Loans Arena.
LeBron James posted a game-high 25 points and 11 assists, while team-mate Kyrie Irving - named the USA Basketball Male Athlete of the Year on Sunday - produced a double-double of his own with 17 points and 12 assists.
But the night, in part, belonged to Cavs point guard Dion Waiters.
Waiters sparkled in the final quarter, where he scored 13 of his 21 points, much to the delight of James.
"He's learning every day," said James. "He's a young guy. He hasn't experienced much in this league, so for him to have a game like he had, we needed it."
Spaniard Marc Gasol was the pick of the Memphis players, finishing with 23 points and 11 rebounds as the Grizzlies crashed to consecutive losses.
It was better news for the Kings, who trumped the Los Angeles Lakers 108-101 in Sacramento for their first win in five outings.
DeMarcus Cousins starred in his second start since returning from viral meningitis, registering 29 points and 14 rebounds at Sleep Train Arena.
Rudy Gay (24) and Ben McLemore (23) combined for 47 points for the Grizzlies (12-15), who trailed 89-83 in the fourth quarter.
The Lakers (8-19) were led by veteran Kobe Bryant (25 points) and Nick Young (26 points).
There was rare joy for the Philadelphia 76ers, who saw off the Orlando Magic 96-88 for just their third win of the season.
The Sixers improved to 3-23 thanks to solid contributions from Michael Carter-Williams and Nerlens Noel on the road.
Carter-Williams had a team-high 21 points, while Noel clocked up 13 points and 12 rebounds.
The Toronto Raptors made it six wins on the bounce after defeating the New York Knicks 118-108.
The Miami Heat ended a five-game home losing streak with a 100-84 win over the Boston Celtics and Anthony Davis' 38 points and 12 rebounds helped the New Orleans Pelicans edge the Oklahoma City Thunder 101-99.
The Washington Wizards were upstaged 104-92 by the Phoenix Suns, the Indiana Pacers accounted for the Minnesota Timberwolves 100-96 and the Brooklyn Nets prevailed 110-105 against the Detroit Pistons.