Brooklyn never trailed and led by 10 points in the first quarter, 15 in the second, 18 in the third and 22 in the fourth to improve to 24-12.
They are closing in on the franchise record of 14 successive victories, set in 2003-04 and matched in 2005-06.
"We held them to 22 points in the first quarter, so we put our stamp on the game in a hurry," Nets coach Jacque Vaughn said.
"We wanted to come out with the right mindset, which we did."
There was no place for Patty Mills, who had played a significant role in the Nets' last outing - a thrilling single-point win over Atlanta on Thursday - but Ben Simmons enjoyed 19 minutes of court time.
LaMelo Ball was Charlotte's outstanding player, with 23 points, seven rebounds and 11 assists.
The Nets lie second in the Eastern Conference.
It was their sixth straight win, and their fifth in a row over San Antonio.
Spurs coach Gregg Popovich had jokingly vowed Doncic would be held under 50 points, and the Mavericks star almost played along.
He was stuck on 49 for half the fourth quarter but made two free throws with 4.5 seconds left to top 50 for the fourth time in his career.
It was his third 50-point outing in his past five games, including a remarkable 60 points, 21 rebounds and 10 assists on Tuesday night in an overtime victory over New York.
Julius Randle scored 35 points and Immanuel Quickley added 27 as the New York Knicks snapped a five-game skid with a 108-88 win over the Houston Rockets, while the Indiana Pacers clung on to beat the visiting Los Angeles Clippers 131-130.
Paul George scored 45 points, the most by a Clippers player this season, on his return to Indianapolis.