Michael Beasley had 17 points and nine rebounds, Udonis Haslem scored 11 points and Jamaal Magloire finished with 10 points and a season-high 12 rebounds for Miami.
O.J. Mayo scored 21 for the Grizzlies, who started a four-game road trip by losing for the 17th time in 19 games. Rudy Gay was held to eight for Memphis, matching his third-lowest output this season.
Miami stayed 3 1/2 games behind Atlanta in the race for the No. 4 seed in the Eastern Conference playoff chase. The Heat
-- who won in Detroit on Sunday and swept a back-to-back for the third time in 16 tries this season
-- also ensured they would keep at least a 1 1/2-game lead on No. 6 Philadelphia, which played later at Portland.
Playing without starting forward Jermaine O'Neal, who sat out as a precaution with a bruised right hip but is expected to be available Wednesday when the Heat visit Indiana, Miami beat the Grizzlies for the first time in the teams' last four meetings.
Miami took command from the opening tap, scoring on its first five possessions for a quick 11-0 lead that matched its best of the season. The Heat also scored the game's first 11 against Atlanta on Dec. 12, a game they eventually lost.
This one was never in danger of slipping away.
Wade scored 11 points in the first quarter, including a highlight-caliber slam to end the period. He took a bounce pass at the foul line and went over an outstretched Milicic
-- taken three spots before him in the 2003 draft -- for a dunk that put Miami up 30-16.
And Wade struck again, perhaps even more dramatically, at the end of the second quarter.
Mario Chalmers reached his hand behind Memphis' Mike Conley for a steal, flicking the ball to Wade. He took four dribbles, looked up at the clock, leaped from just inside the foul line and dunked with two-tenths of a second remaining for an 56-40 Heat edge going into intermission.