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.
Paris Masters 2020: Alexander Zverev says he's 'still smiling' despite losing final, assault allegations
Zverev led by a set against Medvedev in his bid for a fourth Masters title on Sunday, but fell to a 5-7, 6-4, 6-1 defeat.
Medvedev was on top form in a high-quality encounter, winning 5-7, 6-4, 6-1 to secure his first trophy of the season and the eighth of his career.
Paris Masters 2020: Alexander Zverev beats Rafael Nadal in straight sets to set up final against Daniil Medvedev
The German claimed his second successive win over Nadal in impressive fashion, easing to a 6-4, 7-5 victory after Medvedev's earlier 6-4, 7-6 (7/4) win over Milos Raonic.
Djokovic, a winner of 17 Grand Slam titles, had already moved past Sampras' tally of 286 weeks in the top spot in September.
Paris Masters 2020: Rafael Nadal through to semi-finals in comeback win, Diego Schwartzman books maiden ATP Finals place
Nadal claimed a 4-6, 7-5, 6-1 victory over Pablo Carreno Busta, ending his fellow Spaniard's hopes of qualifying for the season-ending tournament in London.
Paris Masters 2020: Rohan Bopanna, Oliver Marach enter men's doubles quarter-finals with hard-fought win
The unseeded Indo-Austrian pair came from behind to defeat their fancied rivals 3-6 6-4 10-8 in the round of 16 tie Wednesday night.
Paris Masters 2020: Rafael Nadal romps to 1000 Tour-level wins; Diego Schwartzman inches closer to ATP Finals debut
The 28-year-old Schwartzman was too strong for France's Gasquet, taking a 7-5, 6-3 victory, and will next face Spanish qualifier Alejandro Davidovich Fokina in the last 16 at Bercy Arena.
Humbert, who is on a seven-match winning streak after winning the Antwerp title last month, missed four match points but battled to a 7-6 (7/4), 6-7 (6/8), 7-6 (7/3) victory.
Paris Masters 2020: Karen Khachanov knocked out in first round as tournament begins despite France lockdown
Tournament organisers had expected to welcome 1,000 fans a day to the event, but instead had to refund the tickets when French President Emmanuel Macron announced France would re-enter lockdown last week.
The winner of this year's tournament will pocket just over 20 percent of the cheque taken home by 2019 champion Novak Djokovic.
Paris Masters to go ahead as scheduled without fans, confirm organisers as France goes into second lockdown
World number two Rafael Nadal, who won a 13th French Open at Roland Garros in Paris just over two weeks ago, is the top seed at the tournament.
Djokovic said his main priority is to remain first in the rankings until at least 8 March next year to break Roger Federer's record for most weeks in the ATP's top spot.
Rafael Nadal has never won the Paris Masters in his career. This year, the tournament is scheduled to run from 2-8 November.