Mavs point guard Luka Doncic scored 18 of his 24 points in the first half, when Dallas essentially put it out of reach, taking a 77-27 lead into the break.
Josh Richardson added 21 points and Tim Hardaway Jr. chipped in 18 for the Mavericks, who had opened the season with two defeats, including a 138-115 loss to the Los Angeles Lakers on the same Staples Center court on Friday.
"This was obviously our best performance of all the games, pre-season and regular season," Mavericks coach Rick Carlisle said.
"We had some uneven effort in the first couple of games. Guys were aware of it. They knew the caliber of our opposition today and they just decided that they were going to be the hardest-playing team in the gym."
Paul George led the Clippers with 15 points and Serge Ibaka added 13.
But they clearly missed Leonard, who needed eight stitches on a cut in his mouth after he collided with Ibaka in the fourth quarter of a victory at Denver on Friday.
Eight of the Clippers' 14 turnovers came in the first half. They opened the third quarter on a 10-0 scoring run, but any momentum was short-lived for a team that coach Tyronn Lue said, "didn't have a lot of pop."
"I think a couple of turnovers early, we missed some shots, they got out and transitioned us early," Lue said. "They had a lot of pop tonight."
Lue, who took over as coach this season after the departure of Doc Rivers, said he didn't think there was anything to be learned from the defeat.
"I think we throw it away, just get back to what has been working," he said. "It's just an exception. It doesn't take away from what we've been working on."
The halftime margin grabbed attention around the league. Former Lakers great Magic Johnson tweeted: "I've never seen anything like that before in the NBA and the Clippers are at home!"