Only Switzerland's Federer (20) and Spain' Rafael Nadal (17) have won more Slams than Sampras and Djokovic.
Federer even called for a portable fan to be repositioned and placed directly in front of him on changeovers as he sat in his chair.
It was the world number two's earliest defeat at the tournament since a fourth round loss to Tommy Robredo in 2013.
Many are saying this a sign that Federer is simply not able to keep up with the top of the sport anymore, but some insist otherwise, blaming his loss on the extremely hot conditions in NY.
Just moments after his big win, however, Millman revealed what was really on his mind - his coming fantasy football draft and whom to take with the second overall pick.
"It was very hot". There was no circulation at all.
"It hasn't come too easy for me and it's very cliche but this is why you play: to be competing at these famous tournaments", the Queenslander said.
Last US men's hope ousted as Del Potro topples John Isner
The world No 1 only won seven points in the entire first set but recovered to secure a 0-6, 6-4, 7-5, 6-7 (4), 7-6 (5) victory. Rafael Nadal jumped over the net to embrace and apologise to Dominic Thiem following their epic five-set US Open thriller.
"It's hard to discount the guy, because he's obviously the greatest of all time, and he's unbelievable, but that one stands out to me", Mark Knowles, a former No. 1 doubles player turned television analyst, said of Federer's loss to Millman.
"John was able to deal with it better". I knew I was in for a tough one.
"I felt like a deer in the headlights at the beginning, to be honest with you". Nearly got to the point where I wanted him to start making shots like that, and I finally got it. The Australian ran his heart out to reach for the shots that Federer did make - be it a drop shot or angled attempts down either flank.
Statistics support the 29-year-old's theory that he needs to be bold. By the end of the match he had even covered 400 metres more than the Swiss. The 20-time Grand Slam champion committed 76 unforced errors, including 10 double faults on a humid day in NY. In the second set, serving for the set at 5-4, 40-15, he failed to convert.
Goffin served for the first set at 5-4 before Cilic went on to win the tiebreaker. It wasn't that he didn't want to be there, but he certainly wanted to get out of there as quickly as possible, trying to win quick points, stubbornly sticking to the same tactics and nearly looking resigned to defeat, even as he battled deep into the fourth set. This is a guy who had never managed to beat a top-10 player, let alone a man who has spent more weeks at No. 1 in the ATP rankings than anyone else. Federer served 10 double faults and committed a frankly staggering 76 unforced errors throughout the match, which helped pave the way for easily the biggest win of Millman's career. "I have so much respect for Roger and everything he's done for the game". I've got a seven o'clock in the morning fantasy draft, so I have to get up for that and hopefully have a good draft.
"I didn't know he had a girlfriend in Stuttgart". "The deputy did a lot of running down to my room, giving me score updates and things like that". Roger had me on a string.
Federer himself summed it up best in his post-match interview. They love him in Japan. he lets them come onto the court and get photos after he trains.