Federer and Rublev had never played each other before but the young Russian broke the 20-time Grand Slam champion in his opening service game and despite being broken back, broke again to soon lead 4-1.
In the fast conditions in Cincinnati, the Swiss star struggled to keep up with Rublev’s aggressive style.
And Rublev never looked overawed by the occasions as he served out the match in just over an hour.
After the defeat, Federer quickly went to his press conference and heaped praise on Rublev.
“He was super clean. Defence, offence, serving well. Didn’t give me anything. He was everywhere,” Federer said.
“So it was tough for me, but excellent match by him. I was impressed.”
Federer will now begin his preparations for the US Open, which starts on August 26.
And the 38-year-old insisted the extra days off could be helpful leading into the final Major of the year.
“I’m happy I came here. I had good practise sessions and two matches here,” he said in his press conference.
“Hoped it would have gone better but the plan is always not to lose first round. The plan is always not to lose second round. The plan is never really here at the weekend. It is [to] try to be there.
“So when this kind of results happens, I don’t know what you can do. You walk away from it and say ‘what’s the plan’. I just walked off the court.
“I’ll speak to the team about it. But I have a few more days off now I’m sure before the US Open. I worked very hard coming into Cincinnati. So I can utilise a couple of days off.
“I’m going to train on exactly what I need to do for the Open and that’s it. It’s very simple. Keep it simple but work hard.”