The late withdrawal of world No2 Andy Murray forced officials to rejig the bottom half of the draw, with Kohlschreiber taking the spot of 17th-seeded Wimbledon semifinalist Sam Querrey.
He won't be taking Kohlschreiber lightly, but Millman knows having hit with Querrey at the All England Club and also watching the American storm through his first two rounds that the tennis gods have smiled on him.
Millman is already guaranteed $US$144,000, doubling his season earnings. Beating Kohlschreiber would earn him US$253,625 - and a centre-court crack at Federer, if the 19-times grand slam champion can back up from his successive five-setters and see off Feliciano Lopez.
Contesting the Open on an injury-protected ranking after adding a groin operation to two shoulder reconstructions, Millman arrived as No235 as he bids to become the lowest-ranked player since 1985 to make the last 16 in New York.
"It does feel more rewarding when you've had your struggles with your body," Millman said.
"It's probably taken me longer to crack it at this level. I've done the hard yards through the Futures tours, through the Challengers tour. It's taken me a long time.
"I'm sure there were tournaments in the middle of nowhere where I kind of questioned whether I really wanted it. But it helps me appreciate these moments each day because it's not every day you're playing the US Open or you're playing a Wimbledon and that makes it really special for me."
A bad back prevented Federer from getting ready for the US Open the way he prefers to prepare for a grand slam tournament. And it's showed so far.
Federer blamed a lack of practice after making an uncharacteristic 68 unforced errors and being forced to go five sets again before coming back to edge a cramping Mikhail Youzhny 1-6, 7-6 (3), 6-4, 4-6, 6-2.
It is the first time in his long career that the 36-year-old Federer has played five-setters in the first and second rounds at a major tournament.
"I knew I was going to maybe struggle early on. Maybe I struggled more than I would have liked. But I'm still in the draw, which gives me a chance. I still believe I'm going to pick up my game and become just more consistent because I'm not playing all that bad," Federer said. "It's just that I'm going a bit up and down in waves throughout the match."
Given that Federer entered the day with a 16-0 career record against Youzhny and a 16-0 mark in the US Open's second round, one might have thought their match would be a mismatch.
Think again.
"He's also a real man who plays tennis," Youzhny noted. "He's not a god."
History was made when American Shelby Rogers beat Australian Daria Gavrilova 7-6 (6), 4-6, 7-6 (5) in 3 hours 33 minutes, setting the record for the longest women's match.
After Gavrilova's backhand sailed long on match point, the 62nd-ranked Rogers raised her arms and then put her hands to her face and broke into tears.
- AAP, AP