A hot topic of conversation before the tournament had been about Nadal's fifth seeding and the prospect of a quarter-final against Roger Federer, followed by a potential semi-final against Murray for the winner of that showdown.
As it happened, the reigning French Open champion did not even make it past the first round, losing in straight sets to Belgium's Steve Darcis, a player ranked 135th in the world.
It was a similar scenario to last year, when Nadal's second-round defeat against Lukas Rosol meant Murray avoided a likely semi-final meeting with the Spaniard, who he has never beaten at the All England Club.
Murray had no such early struggles on Monday, beating Germany's Benjamin Becker 6-4 6-3 6-2, and thoughts of the last four were the last thing on his mind.
The Scot said in a press conference: "It's pretty irrelevant right now. I'm sure for you guys it's very relevant, but for the players, especially me, I have to win at least four more matches before that would even become something I would think about.
"It's obviously surprising. But the consistency that Rafa, Roger and Novak (Djokovic) have shown in the slams over the last five or six years, it's going to be almost impossible to keep that up forever.
"I didn't see any of the match, obviously, because I was playing. But, yeah, it's a surprising loss."
Murray and Nadal are good friends, with the British number one a huge admirer of his rival, and he feels it is a loss for the tournament to see the two-time champion depart in the first round.
"As a fan of tennis, it's probably disappointing that he's out because he's a fun guy to watch, and he brings a lot to the tournaments that he plays in," said Murray.
"He's one of the best players that's ever played, so it's a shame in that respect.
"But I'm not here to worry about all of the other players just now. I have to focus on myself, my matches, try to take care of them one at a time."
Murray had played Becker - no relation to and nowhere near the tennis equal of his countryman Boris Becker - for the first time at Queen's Club two weeks ago on his way to the title there.
And it was apparent then that the German did not have the weapons to pose any real threat providing Murray played at a decent level.
The 26-year-old Murray was stepping out for a competitive match on Centre Court for the first time since his emotional Olympic final triumph over Roger Federer, and there were a few nerves at the start as he was forced to save a break point in the opening game.
Murray had enjoyed extra grass-court preparation after pulling out of the French Open with back problems, and he looked at ease on the slick surface.
The second seed quickly broke the Becker serve and had two chances for a 5-1 lead but Becker saved them and Murray then threw in a sloppy game, ended by a wild double fault, to lose his advantage.
He reclaimed it quickly, though, breaking to take the first set, and from there Murray barely put a foot wrong.
He broke for the only time in the second set to lead 5-3, Becker showing the strain he was under trying to live with his opponent by blazing a backhand long and wide.
The third set was largely one-way traffic and Murray ended the match with a forehand into the corner, his 38th winner.
The 26-year-old next meets Chinese Taipei's Lu Yen-hsun, who ended hopes of an all-British second-round tie by defeating James Ward in four sets.
Murray was happy with his performance against Becker, saying: "It was a good start.
"He's a tough player. I thought it was a pretty high standard match, apart from a few games in the middle of the first set. We had a lot of good rallies. He served well for the first couple of sets."
Murray's victory was his 107th in grand slams, taking him past Fred Perry to become the most prolific British male winner of singles matches at the four biggest tournaments.
Murray trails only Virginia Wade, who won 130 matches, on the British all-time list, and he said: "I didn't actually know that.
"That's nice. The grand slams are obviously the pinnacle of our sport. It's the tournaments I prepare extremely hard for, where you want to try to play your best tennis.
"I guess that shows I've played some of my best tennis at the slams, and hopefully I can continue that."
Murray was watched by a host of famous names, with Monday's Royal Box guests including the Duchess of Cambridge's sister, Pippa Middleton, Formula One great Sir Jackie Stewart, actress Felicity Kendal and athlete Denise Lewis, along with former United States secretary of state Condoleeza Rice and last year's men's doubles champion Jonny Marray.