The 33-year-old from Switzerland needed just 82 minutes to register a comfortable 6-3 6-4 victory at Indian Wells.
Federer, a four time winner of the tournament, was always in charge against the world No 33 who had his serve broken three times during the contest.
Seppi managed to stave off three match points in the ninth game of the second set before succumbing in the next, as the world No 2 recorded his 11th win in 12 meetings over his 31-year-old opponent.
And Federer was pleased to beat a player who knocked him out in Melbourne earlier this year: “It was good to play him right away again and erase it from the memory.
“This was one of those matches where I was happy to get through and happy it was over.”
Also through is three-time winner Rafa Nadal who beat American Donald Young 6-4 6-2.
However, Nadal was clearly not at his best in a match that yielded nine breaks of serve.
The opening set produced a high number of unforced errors, and saw Nadal sneak over the line after leading 5-1.
Nadal said: “It’s true that I had a few mistakes but I was able to find solutions. I’ve played a lot of good tournaments here.
“I am confident and I hope that I can play a good match in the next round.”