The 22-year-old Slovenian was unstoppable from the opening tip-off, scoring 28 points in the first quarter when he made seven of 10 three-point attempts.
"I felt great," Doncic said after his first 50-point game, in which he connected on 65 percent of his shots from the field and 50 percent from three-point range. "I felt energy. The shots were hitting, they were switching, they didn't want me to create, I guess.
"I'm tired as hell right now," the 22-year-old added.
It was the 17th time in Doncic's career that he scored 40 or more points. His previous career-high was 46.
"It was a really fun thing to watch," Mavericks coach Jason Kidd said. "I didn't have to do much, just tried to stay out of the way."
Six of Doncic's top eight scoring performances have come against the Clippers. But even though they have struggled to contain him, Los Angeles stayed in touch. They cut a double-digit deficit to three points in the final quarter, but couldn't get any closer.
The game was a rematch of a 2021 Western Conference first-round playoff series won by the Clippers in seven games.
Thursday also featured the first meeting between the Phoenix Suns and the NBA Champion Milwaukee Bucks since last season's Finals, the Suns producing a convincing 131-107 victory.
Veteran point guard Chris Paul scored 17 points and handed out 19 assists for the Suns, who improved their league-leading record to 45-10.
DeAndre Ayton scored 27 points and grabbed seven rebounds for the Western Conference leaders.
Khris Middleton and Jrue Holiday scored 21 points apiece for the Bucks and two-time NBA Most Valuable Player Giannis Antetokounmpo added 18 points with seven rebounds and eight assists.
"It's a good win," Paul said. "We're just trying to pile up wins. We've just got to keep building."
Golden State were surprised on their own floor by the New York Knicks, who handed the Warriors a second straight defeat 116-114.
Julius Randle led the Knicks with 28 points and 16 rebounds. Stephen Curry scored 35 points with 10 assists for Golden State.
Nets lose 10th straight
The Brooklyn Nets capped a tumultuous day by crashing to a 10th straight defeat, falling 113-112 to the Wizards in Washington.
Hours after confirming they had traded superstar James Harden to the Philadelphia 76ers -- dismantling their "Big Three" of Harden, Kyrie Irving and Kevin Durant -- the Nets couldn't hang on to a nine-point third-quarter lead against the Wizards.
With Durant still sidelined by a knee injury, Irving scored 31 points with five rebounds and six assists to lead the Nets.
But Washington went on a 13-0 scoring run late in the third quarter to seize an 89-78 lead. Thomas Bryant's three-pointer in the fourth made it 100-87 for the Wizards and the Nets couldn't find an answer.
Cam Thomas had 27 points for Brooklyn but missed a potential game-tying three-pointer in the final second.
"We didn't get enough stops," Nets coach Steve Nash said. "Our defense was not good enough."
Raul Neto, making his first start of the season, scored 21 points for the Wizards. Kyle Kuzma had 15 points, 13 rebounds and 10 assists for the first triple-double of his career.
The Nets, eighth in the Eastern Conference, will now be hoping to quickly integrate new arrivals from Philadelphia Ben Simmons, Seth Curry and Andre Drummond.
"We're not taking our foot off the gas," Nash vowed.
Miami strengthened their grip on the Eastern Conference lead with a fourth straight victory, beating the New Orleans Pelicans 112-97.
Jimmy Butler and Bam Adebayo scored 29 points apiece for the Heat, who out-scored the Pelicans 27-18 in the third quarter to build a one-point halftime lead into a 10-point advantage.
Kyle Lowry posted his second triple-double of the season for Miami with 14 points, 11 rebounds and 11 assists.
The Toronto Raptors, fueled by 42 points from Gary Trent Jr., notched an eighth straight victory, downing the Houston Rockets 139-120.