The result: a Raptors-record 11th consecutive victory at the Air Canada Centre.
Lowry scored 32 points, while fellow all-star DeRozan chipped in with 31 and the Raptors topped the Utah Jazz 104-94 to add to their franchise-record home winning streak.
Lowry had sat out Sunday’s loss at Detroit, while DeRozan had played through the flu two nights earlier in a win over Cleveland.
When the duo is firing on all cylinders, they're "extremely dangerous," says DeRozan.
"Especially once we get going, it's easier to get our teammates involved and get them going as well," he said. "We can pick and choose who we want to attack a team from. It's tough to defend a team like that when we get going like that."
Toronto had won 10 games in a row at home once before, but it was stretched over two seasons -- eight games to close 2001-02, then the first two of the following season.
Terrence Ross, meanwhile, added 11 points, while Jonas Valanciunas finished with 10 points and eight rebounds for Toronto (40-19).
Gordon Hayward had 26 points to top the Jazz (28-32) in their fourth straight loss, while Saskatoon-born Trey Lyles finished with six points in 25 minutes.
Lowry and DeRozan had averaged 48 points between them in the previous 10 home wins, and they were superb again Wednesday. DeRozan shot 11-for-15 on the night, while Lowry was 13-for-20.
"For me and him, we try to take some of the attention that we get and make other guys get some open looks and get them going and then we can get ourselves going a little bit," Lowry said. "But us going together is just what we're supposed to do."
Playing their first of seven games in a row at the Air Canada Centre, the Raptors were sluggish through the first half.
"Our give-a-crap level was low, it was very low," coach Dwane Casey said.
But they parlayed a strong third quarter -- they outscored their visitors 33-25 -- into an 85-74 lead heading into the fourth.
The Jazz rallied down the stretch, and when Hayward drained a three-pointer with 4:29 on the clock, it pulled Utah to within 94-90. But Lowry responded with a pair of baskets, and then DeRozan's fast break jump shot with 1:27 to play put Toronto up by eight points in front of a capacity crowd of 19,800 at the ACC.
Lowry's running layup with 59 seconds left put Toronto up by 10 and put the game out of reach.
"We've got to get our mojo going a little bit harder, cuts, passes, screens, everything was dictated by Utah in the first half," Casey said. "They did a good job of dictating whatever they wanted to do to us on both ends of the floor.
"That was the message at halftime."
Casey had kind words for Lucas Nogueira, who provided a spark off the bench with four rebounds and a huge dunk in just four-and-a-half minutes.
"The length," Casey said, on what he brings. "I knew how long (Rudy) Gobert was and it was going to be an issue for (Jonas Valanciunas) and (Bismack Biyombo). I talked to him at shootaroud this morning, just be ready... That's his gift, he came in and played.
"There's going to be times when we mix in some of the young guys. I don't know when... they've just got to be ready."
Lowry led the way with 10 points in a tightly-contested first quarter that saw neither team lead by more than three points.
The Jazz led 26-24 after the first then opened the second quarter with a 12-2 run to take a 12-point lead. The Raptors went on a run of their own, and a three-pointer by Lowry four seconds before halftime sent Toronto into the break with a 52-49 lead.
NOTES: The Raptors host Portland on Friday... The Jazz beat the Raptors 93-89 on Nov. 18.