Novak Djokovic moves one victory closer to becoming the first male player to win the Grand Slam since Rod Laver in 1969.
The Serbian World No.1 lost the second set, but came back strongly to win the remaining sets against Holger Vitus Nodskov Rune.
Andy Murray lost in the first round of the US Open 2021 with a five-set loss to Stefanos Tsitsipas.
Day 1 also features second seed Daniil Medvedev and eighth seed Casper Ruud against French veterans Richard Gasquet and Jo-Wilfried Tsonga, respectively.
Novak Djokovic is seeded number 1 in the US Open and, unsurprisingly, is the strongest favourite to win the crown at the Flushing Meadows.
Pablo Carreno Busta defeated Novak Djokovic in the US Open 2020 and the Tokyo Olympics bronze medal match.
Roger Federer won 41 consecutive matches in the US Open during a streak of five titles from 2004 to 2008.
The US Open has seen fewer streaks of dominance from the likes of Roger Federer, Novak Djokovic and Rafael Nadal.
Ash Barty and Alexander Zverev won the Western and Southern Open tiitle
Djokovic has already won three Grand Slams this year and will be looking to complete a calendar-year Grand Slam at the US Open.