The three-time runner-up had looked impressive in his first two matches but was outplayed in every department by Lopez, who hit 57 winners and made only seven unforced errors in a 7-6 (7/2) 7-6 (7/2) 6-4 win.
Greg Rusedski, Andy Murray and Roger Federer, who did it twice, are the only other players to have denied Roddick a set at the All England Club, Murray the last to do it in 2006.
Despite the disappointment of being sent home, the American had few regrets in comparison to last year, when he was surprisingly beaten in the fourth round by Lu Yen-hsun.
He said: “This year’s a lot easier to deal with than last year, where I felt like I gave it away. I got beat. He came out, he served about as well as someone has.”
Fourth seed and home favourite Andy Murray proved his credentials in last night’s late match, beating Ivan Ljubicic of Croatia 6-4 4-6 6-1 7-6 (7/4).
Defending Wimbledon champion Rafael Nadal must return today to continue his bid to reach the fourth round after his clash with Gilles Muller was affected by the weather.
The world number one had just taken a nervy first set on a tie-break on Court One when the heavens opened at 5.40pm, with play officially called off for the day at 7pm.
The pair will open play on the same court today and the delay could prove to be a blessing in disguise for Nadal, whose last act before the rain was to leave the arena for a medical timeout.
He stumbled to the floor on the ninth point of the tie-break and took longer than usual to get up, although he sprinted off the court to suggest the problem may not be serious and was last night seen walking out of the grounds showing no signs of discomfort.
Richard Gasquet set up a fourth-round clash with Murray by securing a straight-sets victory over Simone Bolelli. Gasquet needed just an hour and 45 minutes to demolish the Italian 6-3 6-2 6-4 on Court 14.
In the women’s, Tsvetana Pironkova produced a major upset at Wimbledon for the second year running as she beat Vera Zvonareva to set up a fourth-round clash with her superstar victim from last year, Venus Williams.
Pironkova, from Bulgaria, has struggled up to live up to the acclaim which followed her straight-sets win over Williams in 2010. But she showed off her class when she beat Russian number two seed Zvonareva 6-2 6-3 on Court Two in a repeat of last year’s semi-final, avenging the result from that match.
Williams, the five-time champion, is determined there will be no repeat of last year’s shock defeat to Pironkova when the pair meet again on Monday in the last 16.
The American looked out of sorts in their quarter-final 12 months ago but was in imperious form yesterday, mercilessly putting Maria Jose Martinez Sanchez to the sword with a 6-0 6-2 win on Court One.
She looked back to her best and has warned world number 33 Pironkova she will need a huge performance to repeat her shock win.