Del Potro broke down in tears as his US Open run came to end with the Arthur Ashe Stadium crowd giving him a standing ovation.
The Argentinian player applauded the crowd and had to compose himself before facing what turned out to be the last game of a match which concluded close to 1:20am on Thursday morning.
"It's something difficult to describe with words. I can lose the match but I will never forget this," said the 27-year-old former world number four who came into the tournament ranked 142 after undergoing a series of wrist surgeries which pushed him to the verge of retirement.
Wawrinka saluted del Potro who had knocked him out of Wimbledon this summer.
"It was an amazing crowd, for sure. There was a lot of support for Juan Martin. It's normal. I expect that.
"He's an amazing champion. He won here. He got so unlucky with all the injuries he had, and the way he's playing right now already, it's amazing. Everybody is happy to see him back at that level."
Wawrinka, a two-time semifinalist at Flushing Meadows, will face Kei Nishikori for a place in Sunday's championship match after the Japanese sixth-seed upset world number two Andy Murray 1-6, 6-4, 4-6, 6-1, 7-5.