Bynum, who tore the medial collateral ligament in his right knee on Jan. 31, rejoins Pau Gasol to give the Lakers a powerful pair of 7-footers up front.
Bynum went 6-of-10 from the floor, made all six of his free throws, and had five rebounds in 25:03. Gasol, often matched against his brother Marc, had 12 points and 13 rebounds.
Kobe Bryant took just nine shots, made seven and finished with 16 points, seven rebounds and four assists in his 29:14 on the court. Trevor Ariza added 12 points in Los Angeles' balanced attack.
Bynum said he's adjusting to playing again.
"I'm feeling a little better, my timing's getting better," he said. "I'm getting back into the flow, getting back into the rhythm."
Lakers coach Phil Jackson noted the progress.
• Andrew Bynum led all Lakers with 18 points in just his third game back from injury, helping Los Angeles sweep the season series against the Grizzlies.
• The Lakers are 1½ games back of the Cavaliers for the best overall record.
• O.J. Mayo scored a game-high 20 points for the Grizzlies, who lost for just the third time in their last eight games.
• The Lakers improved to 24-4 over the last two seasons when Kobe Bryant (16 points in 29 minutes) scores fewer than 20 points.
-- ESPN Stats & Information
"Obviously, that initial game, he was kind of awkward out there, not comfortable," Jackson said. "I think he is much more comfortable doing what he has to do out there.
"Tuesday night's game is his final tuneup before the playoffs."
The Lakers (64-17) are all but mathematically eliminated in the duel with Cleveland (65-15) for best record and end the regular season Tuesday night at home against the Jazz -- their probable first-round opponent.
"We're going into [the Utah game] trying to send them a message," Bynum said.
Bryant, asked whether the Lakers would rather play Utah or Dallas in the opening series, said "It doesn't matter. You're going to have two different styles of play. In terms of physical play, Utah is actually one of the best teams in the league."
O.J. Mayo led the Grizzlies with 20 points, and Marc Gasol had 14 points, eight rebounds and four assists.
Memphis coach Lionel Hollins said the Lakers obviously weren't about to take the same approach as when they lost in Portland two nights earlier.
"They were aggressive. That's all it was, they were very aggressive," Hollins said. "They had a tough loss the other night and they came out and played much harder. They took post-ups out of the game, they double-teamed and zoned up to the post-ups and we struggled to score.
"We went out without any intensity and any aggressiveness and got beat by a much better team that was more focused than we were."
Jackson said he's cut down on G Derek Fisher's minutes over the past few games because he wants him rested for the playoffs. Fisher played 18 minutes against Memphis and scored four points on 2-of-9 shooting. ... Los Angeles went 4-0 to sweep the series against Memphis for the first time since 2002-03. ... Los Angeles was coming off a 106-98 loss at Portland on Friday. Memphis beat Phoenix 106-89 win Friday, the Grizzlies' fifth win in seven games.