The third-seeded Raonic bested Istomin 7-6 (7-3), 6-2 in 89 minutes, successfully defending his 2011 crown at the indoor hard-court event in San Jose.
Raonic fired seven aces and won 86 percent (19-of-22) of his first-serve points in the opening set and went on from there to earn his second title of the young season.
He also took the Aircel Chennai Open in early January.
The unseeded Istomin fell in just his second career ATP final.
Swim Week Miami Beach 2014 [PHOTOS]