DeRozan, making a strong push to be named an All-Star, scored 34 points and grabbed nine rebounds, while Lowry had a triple-double, with 18 points, 13 assists and 10 rebounds.
"At the end of the third period and start of the fourth, we had Michael [Carter-Williams] in with our bench guys, and we weren't able to hold the fort," said Sixers coach Brett Brown, whose team fell to 14-29.
"I give them credit. They guarded the heck out of us. They are a good defensive team. We had a hard time making some shots. You look at the stat line and we didn't turn it over; we made some free throws. They just made a lot of midrange jump shots, and DeRozan, it's fair to consider him an All-Star."
The Atlantic Division-leading Raptors improved to 22-20.
Carter-Williams led the Sixers with 20 points, while Thaddeus Young had 16, and Spencer Hawes collected 14 points and 12 rebounds. Evan Turner scored 13, but shot only 5-for-17, and Hollis Thompson came off the bench for 15.
"They stuck with it," Young said. "They made crucial plays down the stretch, and we went kind of cold. They are a good team. I don't look past them.
"There used to be a point where the Toronto Raptors came in and you thought it could be an easy one. We know they have a lot of key guys who can do a lot of different things. DeMar was big for them, and Kyle Lowry was big also."
Tony Wroten and his sprained right ankle did go through a good portion of yesterday morning's shootaround, but he declared himself less than 100 percent and so sat out his third straight game.
"I'll keep working on it," he said. "I went over plays, shot and tried to keep my ankle loose [at shootaround]. I can run and jump, but it's not 100 percent, yet. We're just going to keep working on it."
There might not have been a happier player in the arena last night than center Dewayne Dedmon. That's because on Thursday, he was told the team would give him another 10-day contract. The move became official yesterday.
"I was just hoping that it was going to happen and when it happened it was like, 'All right, I must be doing the right thing, so I have to keep it up.' I didn't know until yesterday," Dedmon said.
"I feel like I'm pretty good at fitting in. If they keep giving me the opportunity, I just have to keep showing improvement."
On Twitter: @BobCooney76