Under the lights on Arthur Ashe Stadium is an environment where the Scot feels completely at home and he showed it with a brilliant display to defeat big-serving Raonic 6-4 6-4 6-2.
The 21-year-old Canadian is regarded as the best of the next generation but he had no answer as Murray progressed to his eighth straight grand slam quarter-final, where he will face Croatia's Marin Cilic.
Murray hit 31 winners and made only 12 unforced errors as he wrapped up victory in exactly two hours, and the 25-year-old said: "I used a lot of variation tonight [Monday]. Milos has a huge game.
"I had to guess sometimes on the return. I got lucky a couple of times and I hit my passing shots really well tonight [Monday]."
"I knew going into the match that I was going to have to return well," the third seed said. "And then I also had to stay extremely focused and give as few points as possible on my serve away.
"He was always going to come up with some big returns or come to the net a couple of times, get me in tough positions on my serve.
"But I passed really well tonight when I needed to. I kind of made him back away from the net. I had to play extremely solid, and I did that."
After the oppressive heat of Murray's four-set marathon against Feliciano Lopez on Saturday, the conditions could not have been more different.
It was cool and windy with rain in the air, and the match was brought forward because of the poor forecast.
He said: "It just started raining just now, so it was perfect timing to finish.
"When we got told the match was getting moved a bit earlier, it wasn't so much the match getting earlier that was hard - it's knowing there is possibly going to be showers and stops, which can disrupt the rhythm of the match and can make it tough, especially when you're playing against someone with as big a serve as him.
"It's tough to get into a rhythm when there isn't stops in the match. I was glad I managed to get the match done before the rain came."
Raonic was lucky to get through his first-round match against Santiago Giraldo but blasted his way past James Blake on the same day Murray had such a struggle against Lopez.
They had met once before, on clay in Barcelona earlier this year - a match Raonic won - and the 21-year-old certainly does not lack confidence.
He had served 89 aces in his first three matches - substantially more than anyone else in the tournament - and Murray was having difficulty just getting a racquet on the ball in the early stages.
But it was the Scot who had the first break point of the match in the seventh game, only for Raonic to come up with a big serve and forehand.
Raonic came under pressure again in his next service game, though, largely of his own making with two double faults.
This time Murray had three break points and he took the third with a cute forehand drop shot - a tactic that was serving him well.
The third seed's serve was looking in fine fettle as well and he comfortably served out the set, celebrating with a shout of 'come on'.
Raonic was making too many unforced errors to really test Murray and was really struggling to match his opponent from the back of the court.
The British number one's confidence was epitomised by a point in the second game of the second set when, chasing down a Raonic lob, he swivelled on a sixpence and drilled a winner down the line.
As well as beating Murray, Raonic has come close three times to defeating Roger Federer this year and pushed Jo-Wilfried Tsonga to 25-23 in the third set at the Olympics.
But he was making little impression on Murray and the third seed brought up two more break points at 2-2 with a brilliant backhand down the line.
Raonic saved those, one with a delightful touch volley, but a third arrived and this time the 21-year-old netted a forehand.
That was the story of the match for the 15th seed, and Murray created two set points on the Raonic serve with an easy forehand pass.
The Canadian hung on but it was only a temporary reprieve as Murray served out the set to love.
An indication of how well Murray was playing was that Raonic was making more than 70% of his first serves but had still faced nine break points while the Scot had not given his opponent a single chance.
More openings arrived for Murray in the third game of the third set, and again he broke through, Raonic netting a routine backhand and trudging disconsolately back to his chair.
The Canadian had really thought this could be his moment but he was being kept at arm's length by the excellence of Murray, and he faced yet another break point in the seventh game.
The Scot had left Raonic floundering time and again with his dipping passing shots and two more gave him a 5-2 lead and a chance to serve for the match, which he managed with consummate ease.
Raonic said: "He said, 'Sorry, I got lucky a few times.' I said, 'Don't be sorry - it was simply amazing. Keep it up and you'll do well'.
"Considering what I was able to put into the match, to have somebody that took me out of it and neutralised me and took it even one step further... I haven't really felt in that situation too much when I feel like I'm doing things well."
Murray's tally of 31 winners and 12 unforced errors was a reflection of his quality, while he was delighted to deny Raonic any chance of a break.
"On this surface, against a big hitter like him, normally you'll have to save some break points," Murray added. "But I served really smart today, did a good job behind my serve.
"I did the same at the Olympics. I didn't get broken the last three matches I played there. It's really important to serve well the deeper you go in the tournament. It conserves a lot of energy.
"The first round I served really badly, so there were long baseline rallies. It's physically tiring when you're serving at or 29% or whatever I was serving at in the first match. So I was happy with that."