Medvedev fought back to beat Denis Shapovalov 4-6 6-3 6-2 in two hours and 16 minutes, with his greater depth and accuracy in the second and third sets proving decisive.
"I am really happy," world number four Medvedev told the official ATP website.
"This match was the best of the week because Denis was really playing unreal until probably 4-3 in the second set. He dropped his level by maybe two percent and I was able to use it.
"This is one of the best victories when you know your opponent is on top of you, but you try and stay there and do what you can."
Medvedev has now won 15 tour-level titles, with seven of them coming on indoor hard courts.
Meanwhile, Felix Auger-Aliassime overcame Holger Rune 6-3 7-5 to win the Swiss Indoors Basel and lift his third consecutive ATP Tour title.
Auger-Aliassime became the third player to win a title in 2022 without dropping a service game, emulating Taylor Fritz and Nick Kyrgios at Eastbourne and Washington respectively.
He said: "It's been an amazing week. Once again in the final, not getting broken all week… (It's been) a long year, a long stretch of wins, and it's not over.
"So hopefully I can keep going, but right now I'm feeling all the good emotions that come with winning a tournament."