Roddick knocked off his Italian opponent 6-3, 6-2 in the final tuneup before next week's Wimbledon tourney.
The victory could give Roddick some needed momentum heading into Wimbledon. He had failed to get past the quarterfinals this year and was eliminated in the first round at the French Open.
On Saturday, Roddick served five aces and broke Seppi's serve five times.
The win also extended Roddick's 12-year streak of winning at least one tournament per year.