Enes Kanter added 12 points and 12 rebounds for the Knicks (12-12), who snapped a two-game losing streak that saw them fall below .500 for the first time since late October.
Marc Gasol scored 17 points and Tyreke Evans had 15 to lead the Grizzlies (8-16), who lost for the 11th time in 12 games.
The Knicks used a 19-2 run to break open a close game after the teams went into the half tied at 49.
Porzingis scored seven points in the fourth quarter as he struggled from the field for much of the game in his first game back since sustaining a sprained ankle less than three minutes into the team's 115-86 victory over Miami on Nov. 29.
Porzingis, the fifth-leading scorer in the NBA at nearly 26 points per game, shot 8 of 19 from the field Wednesday after starting 5 of 15.
Without the services of shooting guard Tim Hardaway Jr. for the third straight game because of a stress injury in his lower left leg, and with Porzingis off the mark, the Knicks turned to Lee to spark them after Memphis went up big early.
The Grizzlies broke a 17-17 first-quarter tie with a 15-3 run, led by Chandler Parsons, who had 10 points during the stretch.
Lee took over in the second quarter, scoring 12 points, including a 3-pointer with two seconds left in the half. The teams went to the locker room tied 49-49.
NOTES: Knicks SG Tim Hardaway Jr. is expected to miss at least two more weeks while he receives treatment for a lower left leg stress injury, the Knicks announced via Twitter before the game Wednesday. ... New York SF Lance Thomas got the start for Hardaway, replacing rookie SG Damyean Dotson, who started the previous two games in Hardaway's stead. Dotson averaged only 5.5 points in his two starts. Thomas scored eight points against the Grizzlies. ... Memphis fell to 1-4 with J.B. Bickerstaff as interim coach. The team fired former coach David Fizdale on Nov. 27. ... The Grizzlies return home Friday to face the Toronto Raptors in the start of a three-game homestand. ... The Knicks travel to Chicago on Saturday before returning home Sunday to oppose the Atlanta Hawks.