The second seed reached the semi-finals in the previous two Grand Slams after her Australian Open triumph and will now leapfrog Iga Swiatek (22) when the latest rankings are released on September 11th after the New York champion's shock exit on Sunday.
Swiatek fell 3-6, 6-3, 6-1 to former French Open champion Jelena Ostapenko (26) and Sabalenka - who has a 20-2 record at the majors this year - will aim to push on after accomplishing another of her main objectives for the season.
"Reaching the WTA world number one singles ranking is something I've dreamed of ever since I was a little girl when I started playing tennis," Sabalenka said.
"It's an unbelievable feeling to join the amazing list of other WTA players to achieve this and it's a huge honour to be able to call myself the number one."
While Sabalenka will headline the evening session at Arthur Ashe Stadium, reigning men's champion Carlos Alcaraz (20) will face unseeded Italian Matteo Arnaldi (22) in the afternoon as Alcaraz steps up his bid for a third Grand Slam crown.
"I think I'm playing at a good level," Alcaraz said. "I'm feeling really well on court, really comfortable. I always say that I can be better, but right now I'm really happy with the level that I'm playing."
Alcaraz takes centre stage after local favourites Madison Keys (28) and Jessica Pegula (29) clash in the opening match of the day on the main show-court, while German Alexander Zverev (26) meets Italian Jannik Sinner (21) to bring the curtain down on the eighth day.
Over at Louis Armstrong Stadium, American Peyton Stearns (21) will hope to keep her dream run going at Flushing Meadows by knocking out Wimbledon Champion Marketa Vondrousova (24).
Russians Andrey Rublev (25) and Daniil Medvedev (27) will also be in action against Briton Jack Draper (21) and Australian Alex de Minaur (24) respectively, with a tantalising meeting between Ons Jabeur (28) and Zheng Qinwen (20) splitting their matches.
Tunisian Jabeur, dubbed her country's "Minister of Happiness" and a crowd favourite at the US Open, has soldiered on despite having flu as she bids to become the first African woman and Arab player to win a Grand Slam singles title.
"This is a fun tournament. Not fun starting being sick," last year's runner-up said. "I feel like this tournament is testing me and showing me I have a lot of strength, that I can go really far and maybe have a great result here."
