The triumph makes up somewhat for the disappointment of a first-round defeat at Queen's Club for American Roddick 10 days ago.
The former world number one needed only one hour 12 minutes to thrash the third-seeded Seppi as clouds gathered over the seaside town.
Roddick, 29, was given a wildcard into the tournament and went on to secure a first final appearance in 16 months.
He was broken by Seppi in the opening game but then turned the tables and took complete control of the match.
"I think I served 90 per cent in the second set which is a pretty good number, especially given the conditions," said Roddick, who has won at least one title every year for 12 years, a record among active players that he shares with Roger Federer.
"I went from a six-match losing streak to all of a sudden winning a tournament - it is a 180-degree turnaround," added the American, three times a runner-up at Wimbledon. "I am thankful that it went my way this week."
Unseeded Austrian Tamira Paszek won the women’s event after saving five match points and overcoming a leg injury to beat fifth seed Angelique Kerber 5-7 6-3 7-5.
The early games were accompanied by chants from a delegation of Dutch dockers, standing outside a gate close to Centre Court, who were claiming that insurance company Aegon, the principal tournament sponsor, had mishandled their pension fund.
However, the notorious Eastbourne winds carried away their cries before the men were shepherded off by security staff.