Isner put up some initial resistance before falling to the Swiss superstar 7-6 (9-7), 6-3. Federer unleashed seven aces and won 33-of-35 first-serve points in the 81-minute match.
Federer logged his 15th straight win since falling to the 6-foot-9 Isner in the Davis Cup last month. He gained the finals of the $4.7 million Indian Wells event after besting rival Rafael Nadal in two sets Saturday.
Federer pocketed $1 million for his third win of the season and 73rd of his career. He also tied Nadal's record of 19 ATP World Tour Masters 1000 titles.
Isner had downed defending champion and world No. 1 Novak Djokovic in Saturday's semifinals.