Medvedev is now the third Russian man to win a major title after Yevgeny Kafelnikov (1996 French Open, 1999 Australian Open) and Marat Safin (2000 US Open, 2005 Australian Open).
Medvedev is the fifth player to defeat the World no. 1 in a major final to win their first major title, since the ATP Rankings were introduced in 1973. The others are Manuel Orantes (d. Jimmy Connors, 1975 US Open), Ivan Lendl (d. McEnroe, 1984 French Open), Pat Cash (d. Lendl, 1987 Wimbledon) and Stan Wawrinka (d. Rafael Nadal, 2014 Australian Open).
Medvedev has now won 147 tour-level matches on hardcourts since the start of 2018, the most on the men's tour. Djokovic is second on the list with 115 hardcourt victories.
Medvedev has now won his 12th hardcourt tour-level title since the start of 2018, also the highest on the men's tour. Djokovic is next on the list with 10 hardcourt titles. The 12 titles have come in 17 hardcourt finals, also the most on the men's tour.
Djokovic's win-loss record in US Open finals now falls to 3-6, tying Bill Johnston for the most losses in US Open finals in men's tennis history.
Djokovic's winning streak at the slams comes to an end at 27 matches. It was tied for the third-longest such streak among men in the Open Era (since 1968). Djokovic won 30 straight matches at the majors from 2015 to 2016, while Australian legend Rod Laver reeled off 29 straight major match wins from 1969 to 1970. Djokovic himself had a streak of 27 such wins in 2011-12, while Roger Federer had two separate streaks of 27 straight wins in majors, in 2005-06 and 2006-07.
Djokovic remains the sixth player, male or female, since the Open Era began, to win each of the first three majors or a calendar year, after Laver (1969), Margaret Court (1970), Martina Navratilova (1984), Steffi Graf (1988) and Serena Williams (2015). He joins Navratilova and Serena as players who fell short of the Calendar-year Grand Slam, the feat of winning all four majors in a year.
With women's champion Emma Raducanu and Medvedev both having won their first majors, it is the first time there have been first-time slam winners on both the men's and women's side at the US Open since 1990, when Pete Sampras and Gabriela Sabatini won. At any major, the last time it happened was in 2004, when Gastón Gaudio & Anastasia Myskina won the French Open.
This is Djokovic's first loss in a major this season after dropping the opening set. His 10 wins at majors this season after dropping the opening set are the most by a man in single year since the start of the Open Era. Four of those wins came at this US Open itself.
With Dominic Thiem earning his first major at last year's US Open, this is the first time there have been back-to-back first-time men's major winners at the US Open since 2000-01 (Safin and Lleyton Hewitt).
Medvedev is the second player to beat Djokovic in straight sets in a US Open final after Federer, who beat the Serb in 2007 in his first major final.
At 25 years old, Medvedev is the youngest active men's major champion. The only other active men's player currently under 30 with a major singles title is 28-year-old Thiem.
Medvedev is now the joint-tallest men's major champion in the Open Era, matching Juan Martin del Potro (2009 US Open) and Marin Cilic (2014 US Open). He equals the tallest player to defeat Djokovic at a major, joining Sam Querrey, who upset Djokovic in the third round at Wimbledon in 2016.
(Stats courtesy of ESPN's Statistics & Information Group)