It took over four hours, but second-seeded Federer finally broke Roddick's serve for the first time to cement his 5-7, 7-6, 7-6, 3-6, 16-14 victory.
In front of Wimbledon legends Pete Sampras, Rod Laver, and Bjorn Borg, Federer captured his 15th Grand Slam title, besting the mark previously set by Sampras.
Sixth-seeded Roddick came tantalizingly close to his first Wimbledon title in three tries, but could not overcome a second-set collapse that saw him squander three chances to go up two sets to none.
While the match featured few long rallies, both men offered a master class in the service game. With the exception of a throwaway fourth set, Federer's serve kept Roddick off balance all day, resulting in a career-high 50 aces.
Roddick controlled the first two sets, but failed to convert on an easy volley at the net during the second set tie-break, opening the door for Federer, who wasted no time in getting back into the match by ripping off six straight points to take the critical set.
In the final set, the longest in a Wimbledon men's final, Federer seemed to hone in on Roddick's serve, dropping a few close games before finally breaking the American for the match.
The fifth set of a Wimbledon final cannot end in a tiebreaker.
"It was a crazy match, an unbelievable end," Federer told onlookers following the match. "My head's still spinning."
In defeat, Roddick thanked a supportive crowd at the All England Club, and apologized to Sampras for failing to hold Federer back from his record-breaking Grand Slam.
Roddick earned the respect of the London crowd after his semi-final rout of British fan favorite Andy Murray days before.
The two exhausted players joked during the trophy presentation, as Federer told Roddick he shared his hurt at losing a Wimbledon final. Roddick was quick to reply that Federer already had five titles to look back on when he lost last year in an epic final to rival Raphael Nadal.
Nadal did not defend his title this year, pulling out of Wimbledon at the last minute due to injury.
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