Raducanu, 21, meets fellow Grand Slam champion Kenin in their first-round match at around 23:30 BST (18:30 local time).
Three other Britons – Katie Boulter, Jack Draper and Dan Evans – also play on day two of the final major tournament of the 2024 season.
A lot of the attention will again focus on Raducanu, who stunned the world by winning the title in New York as a teenage qualifier.
A year later, Raducanu lost in the first round as she dealt with the scrutiny which followed her seismic success, and missed last year’s tournament after wrist and ankle operations cut short her season.
She has moved back into the world’s top 75 after an encouraging run to the Wimbledon fourth round in July, but has only played one tournament since, when she reached the Washington quarter-finals.
“I love this tournament and I have amazing memories from it. It’s a great feeling to be back and to see my face on the wall and see name on the trophy,” Raducanu said about her return to Flushing Meadows.
“I’m still only 21 so I have a lot of years to win this title and the other Slams. I’m feeling good.”
What else is happening on Tuesday?
British women’s number one Boulter, seeded 31st, starts against Belarusian qualifier Aliaksandra Sasnovich at 16:00 BST.
Draper, who is the British men’s number one and seeded 25th, takes on China’s Zhang Zhizhen at about 19:00 BST as the post-Andy Murray era begins in the men’s singles.
Former world number one Murray retired after the Olympic Games last month, when he played alongside Evans in the doubles.
Evans, 34, faces Russian Karen Khachanov at about 18:00 BST as he aims to find joy in a difficult year, which has brought wins in just four singles matches on the ATP Tour.
A host of big names are also in action.
Italian men’s world number Jannik Sinner plays for the first time since it was revealed he had tested positive for a banned substance.
The 23-year-old, who was cleared of fault or negligence by a tribunal last week, faces American hope Mackenzie McDonald on Arthur Ashe Stadium at about 19:30 BST.
Poland’s Iga Swiatek, who is the leading women’s player, opens up Tuesday’s action on Ashe when she plays Kamilla Rakhimova at 17:00 BST.
In the night session, which starts at 00:00 BST on Wednesday, Spanish third seed and 2022 champion Carlos Alcaraz plays Australia’s Li Tu, with sixth seed Jessica Pegula taking on Shelby Rogers in an all-American clash afterwards.
Russia’s 2021 men’s champion Daniil Medvedev, recent Wimbledon runner-up Jasmine Paolini and American 11th seed Danielle Collins, who will retire at the end of the season, are among the players in action on Louis Armstrong Stadium.
Greek 11th seed Stefanos Tsitsipas and Kazakh fourth seed Elena Rybakina feature on Grandstand before Raducanu’s match.