Jrue Holiday led the Sixers with a game-high 22 points.
The Grizzlies put the game out of reach with a pair of Tony Allen free throws that followed Rudy Gay's three-pointer that pushed the Memphis lead to 86-74 with 1 minute, 47 seconds remaining.
The Sixers will play their last game before the all-star break on Wednesday at Houston. On the plus side for them is their 7-1 record in the second game of back-to-backs this season. After the Houston game, the Sixers don't play again until Tuesday, when they face the Pistons in Detroit.
Already missing center Spencer Hawes (Achilles tendon), the Sixers learned earlier in the day that they also would be without Elton Brand. The power forward, who suffered a sprained right thumb against Miami earlier in the month and missed a pair of games, reinjured the thumb in the closing moments of the Sixers' loss Sunday at Minnesota.
In Brand's place, coach Doug Collins gave Andres Nocioni his first start of the season, hoping that Nocioni might provide an infusion of energy into what has been of late a sluggish offense.
But rather than running and gunning, the Sixers' early offense was almost nonexistent. The team scored just 10 points in the quarter, its worst showing in the first quarter of a game to date.
The Sixers connected on just 4 of 20 field goals in the quarter. Their poor shooting contributed to an 18-0 Grizzlies run that gave Memphis a 27-7 lead late in the quarter before the hosts' lead reached 30-9.
Former Sixer Marreese Speights, traded to the Grizzlies on Jan. 4, scored six of his 12 points in the first quarter.
But as bad as the Sixers were offensively in the quarter, they stepped it up in the second and got right back in the game behind the scoring of Holiday.
Scoreless in the first quarter, Holiday found his stroke in the second when he scored 13 of the Sixers' 32 points.
Holiday's three-pointer with 2:30 remaining in the half concluded a 15-2 Sixers run that cut the Grizzlies' lead to 43-40.
Probably due to the Grizzlies' substantial size advantage along the front line, the Sixers did not start Nocioni in the second half, opting to go with the bigger Tony Battie. For the game, the Sixers didn't get much out of either player - the two combined for just two points and seven rebounds.
Contact staff writer John N. Mitchell at jmitchell@philly.com or @JmitchInquirer on Twitter.