The giant Russian, 24, has now won 10 consecutive matches following his title earlier this month at the Paris Masters and his victory will taste sweet a year after a winless debut in London
It was a case of third time lucky for the Dutch-Croatian fifth seeds, who lost their first two finals, in Marseille and at the US Open, earlier in the year.
ATP Finals 2020: Daniil Medvedev overcomes Rafael Nadal in thrilling semi-final, sets up title clash against Dominic Thiem
Nadal, who has never won the elite event in his illustrious career, faltered when serving for the match in the second set and was beaten 3-6, 7-6 (7/4), 6-3.
Novak Djokovic, five-time winner finishes second in Group Tokyo 2020 behind Medvedev and will play third-seed Dominic Thiem in the semi-finals on Saturday.
ATP Finals 2020: Nadal earns hard-fought win over Tsitsipas to reach semi-finals; Rublev downs Thiem in dead-rubber
Nadal, whose haul of 86 singles titles includes just one on indoor hard courts, is chasing the biggest prize missing from his resume at the eight-man elite event.
ATP Finals 2020: Medvedev downs Djokovic to reach semi-finals; Zverev keeps hopes alive after beating Schwartzman
Daniil Medvedev secured a spot in the semifinals of the season-ending tournament by dominating five-time champion Novak Djokovic 6-3, 6-3 Wednesday for his second straight win of the group stage.
ATP Finals 2020: Dominic Thiem secures victory over Rafael Nadal; Stefanos Tsitsipas outlasts Andrey Rublev
Nadal, who lost the 2010 and 2013 finals of the event, has to beat Tsitsipas in his last group match to reach the semi-finals of the prestigious season-ending tournament.
The world number one wobbled at the start of the match against the diminutive eighth seed, making his debut at the elite eight-man event but recovered to win 6-3, 6-2.
ATP Finals 2020: Rafael Nadal outclasses Andrey Rublev in straight sets; Dominic Thiem beats Stefanos Tsitsipas
US Open champion Thiem stumbled after winning the first-set tie-break but found his range again to win 7-6 (7/5), 4-6, 6-3 and seize the early initiative in Group London 2020.
ATP Finals 2020: Novak Djokovic vies for sixth crown, Rafael Nadal first as London hosts final year-ending tournament
London hosts its 12th and last ATP Finals tournament headlined by Novak Djokovic and Rafael Nadal but with empty stands. The Serb is seeking a sixth title while the recently crowned French Open winner Nadal is going for his first.
Djokovic said the biggest concern was the unpredictability of the 2021 calendar, with decisions taken out of the hands of the sport's administrators as a result of Covid-19.
The season-ending ATP Finals will be played at the O2 Arena in London for the last time this year. We look at the participants, the schedule and history of the tournament in London.
ATP Finals 2020: Rafael Nadal in same group as defending champion Stefanos Tsitsipas, US Open winner Dominic Thiem
World number one Novak Djokovic will face Daniil Medvedev, Alexander Zverev and Diego Schwartzman in the group stages of the final edition of the tournament in London before it moves to Turin next year.
Medvedev's first final since last year's ATP Tour Finals saw him come from a set behind to beat Alexander Zverev 5-7, 6-4, 6-1 at Bercy Arena on Sunday.
Football, rugby, tennis and horse racing are among the other sports that will benefit from high-profile events being allowed to continue behind closed doors.
ATP makes changes to COVID-19-affected schedule, remains hopeful of fans attending season-ending Finals
The season-ending ATP Finals in London are still slated for 15-22 November, without spectators, but the men's tennis body “remains hopeful” that will change and some fans will be allowed to attend.
Coronavirus Outbreak: WTA Tour working on better pay for lower level players, considers extending 2020 season
The tennis season screeched to a halt in early March due to the virus, leaving players in the lowest tiers without any opportunity to earn their livelihoods.