Despite not replicating the free-flowing tennis of previous rounds, Federer dug deep to win big points. He broke the 45th-ranked Seppi for the first time at the fifth attempt in the decisive game.
“Of course it's a special moment for me, to win here for the eighth time before Wimbledon. It doesn't happen without making an impression,” Federer said.
The 17-time Grand Slam winner sealed his 15th title from 20 finals on grass and his 86th career title from 130 finals overall. Lleyton Hewitt is next on grass with eight titles.
Seppi was in the final after Kei Nishikori withdrew from their semifinal with a calf injury — and Gael Monfils pulled out of the quarterfinal with a knee problem — but the Italian showed no apparent lack of match fitness.
Seppi missed three break points in the first set, including two set points that Federer defended with two successive aces.
“He played better at the decisive moments and deserved to win in the end,” said Seppi, the first Italian to play the final at Halle since the tournament began in 1993. “I'll take some good memories with me.”
It's Federer's fourth title of the season after wins at Brisbane, Dubai and Istanbul, and a timely boost for Wimbledon eight days before the tournament begins. Federer's only losses in the final at Halle came against Lleyton Hewitt in 2010 and Tommy Haas in 2012.
Top-seeded Murray, who was contesting his 50th career final, also won the event in 2009, 2011 and 2013. He joins John McEnroe, Boris Becker, Andy Roddick and Lleyton Hewitt as a four-time winner of the event.
It was Murray's third title of the year, following victories in Munich and Madrid. Earlier Sunday, the third-ranked Murray completed a 6-3, 7-6 (4) semifinal win over Serbia's Viktor Troicki after rain stopped play Saturday.
Angelique Kerber beat sixth-seeded Karolina Pliskova 6-7 (5), 6-3, 7-6 (4) in the final of the Aegon Classic in Birmingham, England, to clinch her first grass-court title.
The big-serving Pliskova had 11 aces but Kerber's ability to contain this threat, along with greater flexibility in longer rallies, eventually turned the match the German's way.
Although Kerber made the first break of serve immediately, she was later unable to convert the four set points it had made possible. After Pliskova broke back, narrowly sneaked the first set, and broke again early in the second set, Kerber seemed out of the match against the dominating Czech.
But Kerber dominated for the next hour, patiently constructing winning rallies and creating two breaks in the second set with another in the third.