Brooklyn never trailed while snapping a 10-game losing streak to Orlando that dated to 2009.
E'Twaun Moore led the Magic with 18 points, and Arron Afflalo finished with 12.
The Nets dominated inside, with Lopez and Blatche pushing around Orlando's young front line. They also got a lift from their bench, with Brooklyn's reserves outscoring their counterparts 55-18 for the game.
Orlando lost its third straight game after starting 2-0. It also tied a franchise-low with four made free throws, compared to 16 for Brooklyn.
The teams play each other again Sunday in Brooklyn, the second of four meetings this season.
The short-handed Nets played without swingman MarShon Brooks, who twisted an ankle during the morning shootaround. So Brooklyn coach Avery Johnson went deeper into his roster, giving veteran Jerry Stackhouse his first minutes of the season.
Stackhouse responded by scoring 11 first-half points to make up for slow starts by Joe Johnson and Deron Williams.
Lopez also went to work early and often in the post, opposite a timid group of Magic big men. He scored 11 of the Nets' first 19 points as they built as much as a 16-point lead in the opening 24 minutes.
That lead passed 30 points early in the fourth quarter. The Nets also held a 48-35 rebounding edge for the night.
Meanwhile, the Magic didn't seem nearly as comfortable in their half-court sets at the outset and were hampered by careless turnovers.
Sixth-man J.J. Redick was visibly frustrated at times, barking at his younger teammates when they failed to move the ball swiftly enough during their offensive sets.
Orlando's remaining reserves also failed to provide a lift, collectively scoring just four points in the first half.
NOTES: Magic PG Jameer Nelson sat for the fourth straight game with a strained right hamstring/groin. Coach Jacque Vaughn said the team co-captain was "making positive steps in the right direction." ... Nets F Gerald Wallace missed his third straight game with a sprained left ankle.