He won by a 7-6 (7/4) 6-4 6-3 margin, while Britain's James Ward lost in four to Yen-Hsun Lu.
The 2002 champion Lleyton Hewitt, unseeded this year, displayed his customary tenacity to see off the 11th-ranked Stanislas Wawrinka in straight sets on Court One in the final men's match of the day, claiming a superb 6-4 7-5 6-3 win.
The well-respected Nicolas Almagro needed the minimum sets to get rid of Jurgen Zopp but Lukas Rosol, who pulled off one of the biggest upsets in the history of the tournament by beating Nadal last year, was unable to make it through to the second round on Monday as he fell to a five-set defeat against Germany's Julian Reister.
Serbia's 14th seed Janko Tipsarevic lost to a familiar face as he bowed out early, with Davis Cup team-mate Victor Troicki taking his scalp, earning a 6-3 6-4 7-6 (7/5) win.
Jurgen Melzer had provided the first minor shock of the day, beating 30th seed Fabio Fognini 6-7 (5/7) 7-5 6-3 6-2 on Court 12.
Giant Pole Jerzy Janowicz proved why he is being tipped to mount a semi-final challenge as he crushed British debutant Kyle Edmund 6-2 6-2 6-4 on Court Three.
Marin Cilic avoided a potential upset by beating Marcos Baghdatis 6-3 6-4 6-4 while Mikhail Youzhny overcame Robin Haase to seal his place in the second round.
Sergiy Stakhovsky beat Brazil's Rogerio Dutra Silva 6-4 6-0 6-4 to set up a second-round clash with Federer, who already looks like he will take some stopping this year.
But it was the departure of Rafael Nadal that caused the major stir on the opening day of play at this year's Wimbledon.
While last year's men's finalists Federer and Andy Murray cruised through their first-round encounters in straight sets, eight-time French Open winner and two-time SW19 champion Nadal was on Monday night poised to board a plane back to Majorca.
The 27-year-old fifth seed was a loser in three sets, 7-6 (7/4) 7-6 (10/8) 6-4, against the unheralded Steve Darcis from Belgium, who defied his ranking of 135th in the world to produce the performance of his life.
That Nadal appeared to be suffering from the knee injury which cost him seven months of his career was a moot point, with the Spaniard refusing to talk about it.
"For me, there were not a lot of things good, but I congratulate Darcis who played well. This is not the right day (to talk about injury). I tried my best in every moment, but this was not right for me," Nadal said.
"I tried my best and congratulate the opponent. It is not a tragedy, it is sport."
For Federer, the only thing bothering him was the weather.
Beginning his quest for a record eighth title on the grass, the 31-year-old needed just one hour and eight minutes to topple Victor Hanesku 6-3 6-2 6-0.
Federer looked classy without having to push himself too hard on Centre Court. Much tougher clashes are to come.
"The longer the match, the longer you spend on Centre Court - it's not a bad thing," Federer said. "That's what I was thinking today. It went by very quickly.
"It was cold. I'm happy to get out of there early and quickly so it was a perfect day."
Ward's compatriot, Murray, had better luck against Benjamin Becker.
Murray became a little sloppy after a fine start but once he had the first set in the bag he did not look back, winning 6-4 6-3 6-2.
"I thought it was a good match and it was a good start for me. He played some solid tennis especially the first two sets and then the third set I started to play better," Murray said.
"It was a tough start for me, he is a very good grass player. I was ready and to win in three sets was a good start. There's always nerves at the start of a grand slam and I'm glad to get it out of the way and hopefully I can improve as it goes on."