The Nets buried the Knicks under two big second-half runs and put six players in double figures in a strong showing in front of new general manager Sean Marks, who was hired Thursday.
Lopez shot 13 of 23 from the field and added eight rebounds in dominating twin brother Robin, who had 10 points and seven boards.
Carmelo Anthony had 22 points, seven rebounds and six assists for the Knicks. Interim coach Kurt Rambis continues to say the playoffs are the Knicks' goal, but they may have blown any shot of that by losing 11 of their last 12 games since they were 22-22.
They've dropped both games under Rambis, who took over when Derek Fisher was fired Feb. 8.
The Knicks led by two at halftime and by five early in the third before the Nets stormed ahead with a 20-2 run for a 74-61 lead. Brooklyn shot 12 of 19 in the period (63 percent) and scored 34 points to take an 84-76 advantage to the fourth.
New York cut it to three in the fourth before the Nets put it away with a 16-2 surge, with Lopez throwing down one dunk and feeding Thaddeus Young for another as the lead grew to 102-85 with about 5 1/2 minutes to play.
Knicks: The Knicks have lost four straight in Brooklyn, their longest road losing streak in the series since the Nets won seven in a row in New Jersey from March 9, 2001, to April 2, 2004. The overall series is tied 91-91. … Rambis faces the last team he coached Saturday when the Knicks visit Minnesota. He was 32-132 in two seasons with the Timberwolves from 2009-11.
Nets: Brook Lopez moved past Richard Jefferson (8,507 points) into third place on the Nets' career scoring list. With 8,527 points, he trails Buck Williams (10,440) and Vince Carter (8,834). … The starting five of Lopez, Young, Joe Johnson, Sloan and Wayne Ellington made its 18th straight start, longest streak for the Nets since Johnson, Deron Williams, Paul Pierce, Mason Plumlee and Shaun Livingston started 19 straight games in the 2013-14 season.
Knicks: Visit Minnesota on Saturday.
Nets: Host Charlotte on Sunday.