The setback marked their 25th straight loss. The record of 26 consecutive defeats is held by the 2010-11 Cleveland Cavaliers.
While the Sixers appear destined for an NBA futility record, the Spurs (54-16) look like a team destined to win a fifth league title.
Even without all-star point guard Tony Parker (Achilles soreness), San Antonio coasted to its league-best 14th straight victory.
Reserve forward Austin Daye made 6 of 10 three-pointers en route to a game-high 22 points. Tim Duncan, a future Hall of Famer, added 19 points even though he sat out the fourth quarter. The Spurs had five double-digit scorers and led by as many as 24 points early in the fourth period.
"I think our recent performances against Indiana, the Knicks, Memphis, we played good teams tough," Brown said. "Tonight you saw just a very well-oiled machine pick us apart a lot of times."
Point guard Michael Carter-Williams and power forward Thaddeus Young scored 17 points apiece for the Sixers.
The rebuilding franchise hired Brown in August to bring the Spurs' winning mentality to Philadelphia.
Monday marked the first time he faced his former team at the Spurs' arena.
"I truly didn't even know how to get to the other locker room," Brown said. "I had no idea. In my 12-something years here, I had never been to that side of the building. I went to a whole other part of our neighborhood that I didn't know existed and couldn't even find it."
Former Spur Bruce Bowen embraced Brown before the coach's pregame news conference outside the visitors' locker room. As the two chatted afterward, Parker came up for an embrace.
Several of San Antonio's players made their way over to Brown on the court before the game. Duncan pointed toward him during introductions. Then shooting guard Danny Green gave him a big hug before the start of the third quarter. And Duncan, Manu Ginobili, and Brown shared a group hug near center court after the game.
"A significant part of my basketball life was spent here with so many incredible memories," Brown said. "You know, elite memories, and to come back here . . . on this court - this city is special."
Brown said earlier Monday that he wanted the Sixers to pay attention to everything San Antonio did during the game.
"You are going to look down and see Patty Mills swing a towel," he said. "You are going to watch people go help people off the floor. You are going to see Ginobili gather a team at a free-throw line and make sure they understand what defense or offense they are going to be in going down the floor. You are going to see [San Antonio coach Gregg Popovich] get stuck into somebody and that somebody is going to allow him to coach him."
The Spurs displayed great ball movement. They basically put the game away with a 22-2 run to make it a 45-24 game with 7 minutes, 11 seconds left in the second quarter.
Popovich believes Brown is the right person to lead the Sixers' projected three-to-five-season rebuilding project.
"He's as tough-minded as the environment that exists there in Philly," Popovich said of a man he considers one of his best friends. "He's a very focused individual with great competitive, unbelievable fiber. . . . He's a winner in life in a whole lot of ways."
Popovich said he "feels badly" for Brown because of the season he's going through.
"But I don't need to feel sorry for him, because he'd be angry if he knew I felt sorry for him," Popovich said. "He doesn't want anybody to feel sorry for him. He understands that he's living a dream, doing what he loves to do, and is more fortunate than 99.9 percent of the people on the planet."