Kentavious Caldwell-Pope paced the Lakers with 24 points. Los Angeles rookies Lonzo Ball (17 points, eight rebounds, six assists) and Kyle Kuzma (19 points) played well in their Madison Square Garden debuts.
Kuzma hit a 3-pointer with 23.9 seconds left to tie the game at 99, but New York's Michael Beasley had two baskets and an assist on a Doug McDermott layup during a 69-second run in overtime to give the Knicks a six-point lead they would not relinquish.
After scoring 29 points in the first three quarters, Porzingis went cold for much of the fourth quarter until hitting a fadeaway with just over two minutes left to give the Knicks a five-point lead. He scored on another fadeaway on the next possession.
New York (14-13) rebounded from an uneven first half to claim a six-point lead minutes into the second half on a Porzingis 3-pointer, but the Lakers battled back and the teams exchanged the lead a half-dozen times in the quarter.
Porzingis had nearly half of New York's 25 first-quarter points, scoring 12 on 5 of 8 shooting while adding four rebounds. He finished with 11 rebounds and five blocked shots.
Los Angeles (10-16) led by as much as seven in the first quarter before building a double-digit lead in the second quarter. The Knicks gradually cut into the deficit and eventually overtook the Lakers with 1:22 left in the half, leading 47-46, but Los Angeles claimed a 51-50 halftime lead.
Enes Kanter had 14 points and 11 rebounds for New York. Beasley and Knicks rookie Frank Ntilikina each had 13, a career high for Ntilikina.
Brook Lopez had 14 points for the Lakers, but second-year forward Brandon Ingram had one of his worst games, shooting 2 of 12 from the field while scoring five points and committing five turnovers in 41 minutes.
NOTES: The Lakers had their two-game winning streak snapped. They had two other two-game winning streaks on the year. ... The Knicks improved their home record to 13-5; they are 1-8 on the road, the lone win coming at defending Eastern Conference champion Cleveland. ... Knicks SG Tim Hardaway Jr., who is sidelined due to a lower left leg stress injury, attended the game in a large walking boot. He is scheduled to be re-evaluated next Tuesday. ... The Lakers conclude their four-game road trip on Thursday in Cleveland to face LeBron James and the Cavaliers. ... The Knicks head to Brooklyn on Thursday for a matchup with the Nets, their second of the year.