David Villa and New York City became the first visiting team to win at Orlando City Stadium, while LA Galaxy stayed hot in MLS.
Spain's all-time leading goalscorer Villa bagged a brace as New York ended Orlando City's unbeaten streak at home with a 3-0 victory on Sunday.
Since moving into their new stadium at the start of the season, Orlando had gone six matches without defeat at the 25,500-seat arena.
But New York conquered the Orlando fortress and beat their Eastern Conference rivals for the first time in seven meetings thanks to Villa, who opened the scoring in the 14th minute.
The referee pointed to the penalty spot when Orlando captain Kaka handled the ball inside the area and skipper Villa converted.
It got better for Orlando 21 minutes later after Rodney Wallace slid in and tucked the ball away at the back post.
Orlando had the chance to reduce the deficit just past the hour-mark but leading scorer Cyle Larin cannoned his penalty into the post.
And Villa made sure of the win eight minutes from time – rounding the goalkeeper for his eighth goal of the season – ending New York's two-game winless run.
Giovani dos Santos was on target as the in-form Galaxy overcame Minnesota United 2-1.
Scores were level after Christian Ramirez cancelled out Dos Santos' 38th-minute opener, but the former turned the ball into his own net with six minutes remaining to gift the Galaxy three points.
The Galaxy have now won back-to-back games, while they are unbeaten in four matches.
Meanwhile, New England Revolution came from behind to beat Columbus Crew 2-1.