The world No1 will face the British ace in the semi-finals after they both won on a day of drama at Flushing Meadows.
Murray stormed to a four-set win over Juan Martin del Potro, while Nadal came from a set down to beat Mardy Fish 3-6 6-1 6-4 6-2.
It is the first time either star has reached the last four in New York.
And Nadal said: “I am very happy to be in the US Open semi-finals for the first time.
“This court has always been very hard for me.
“Andy is doing very, very well. I expect a very tough match.”
Andy Murray is now 7/1 with SunBET to win the US Open. He's 3/1 to beat Rafael Nadal in the semi-final.