Orlando City SC were shock 2-1 extra-time losers to the Fort Lauderdale Strikers of the NASL.
Jose Angulo gave the Strikers a good start in the 12th minute, picking up a through ball and beating Orlando goalkeeper Earl Edwards.
Orlando would level just three minutes later, with Kevin Molino slicing through the Ft. Lauderdale defense and calmly chipping in past Diego Restrepo.
However, Molino and Maicon Santos of the Strikers were both sent off in the 67th minute to force both teams to finish with 10 men.
The match went to extra time and the Strikers scored just before the game was to be decided on penalties when Victor Giro scored after a quick free kick to give his team surprise passage to the quarters.
The Houston Dynamo beat Sporting Kansas City 3-1 to reach the quarterfinals of the U.S. Open Cup.
The Dynamo got things started early, when Abdoulie Mansally played a perfect cross in front of the SKC goalmouth and Mauro Manotas slid in to poke the ball past Alec Kann.
Houston doubled its lead 10 minutes into the second half after a corner kick flew past the goal but was redirected back in front by Andrew Wenger and Alex headed home.
Sporting got on the scoresheet minutes later when substitute Brad Davis made an instant impact by knocking home a Diego Rubio cross that was deflected in front of goal.
Man-of-the-match Manotas added an insurance goal in the 84th minute to put an SKC comeback out of reach for good.
- U.S. Open Cup (@opencup) June 30, 2016
The New York Red Bulls gave up an early lead to lose 2-1 to the Philadelphia Union in the round of 16.
New York opened the scoring in the 17th minute after a Sacha Kljestan free kick was poorly cleared from the Philadelphia penalty area and Mike Grella smashed home.
Grella was the man on the defensive end too, disrupting the Union in midfield and stopping more than one counter-attack single-handedly.
The Union levelled early in the second half when Chris Pontius got on the end of a through ball from Ilsinho and calmly slotted home past Ryan Meara.
Five minutes later, the goal makers were at it again as Ilsinho found a wide open Pontius in front of the net and he volleyed a perfect cross home to make it 2-1.
The New England Revolution rallied twice to beat NASL team New York Cosmos 3-2.
The Cosmos got on the board first, when Ruben Bover finished a nice team move to put New York up 1-0.
The Revs didn't wait long to counter, thought, as Teal Bunbury levelled the score at one apiece right before the break with an assist to Diego Fagundez.
Juan Arango found Sebastian Guenzatti just after half-time and he knocked the lofted pass in to put the Cosmos back on top.
It was all Revs from there, though, as recent addition Kei Kamara levelled for the visitors in the 75th minute and Bunbury added his second in the 83rd minute for the win.
In Wednesday's other matches, FC Dallas defeated the Colorado Rapids 2-1, while Raul Mendiola's early goal helped the LA Galaxy to a 1-0 win over the Portland Timbers.