Playing his third final in as many tournaments, the Russian was too good for Goffin in a 7-6 (7-3) 6-4 victory in Cincinnati on Sunday.
Medvedev holds a 14-2 win-loss record during the North American hard-court swing, an excellent run of form ahead of the US Open.
Having beaten world number one Novak Djokovic in the semi-finals, the ninth seed made a flying start to the decider, racing out to a 4-1 lead.
However, Goffin – the 16th seed – responded to break back, only to lose all five of his points on serve to drop the tie-break.
Medvedev capitalised on a poor start to the second set by the seemingly deflated Belgian as Goffin sent a forehand into the net to be broken to 15 in the opening game.
Just as Medvedev looked to be cruising – he held to love in his first four service games of the set – he had to come from 15-40 down when serving for the match, closing out his maiden Masters crown and fifth ATP Tour title.
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