The WTA announced Williams' withdrawal from the event that starts on October 23 on their Twitter feed, posting a video of Williams herself explaining the decision.
"Hey everyone in Singapore," Williams said. "I'm really, really bummed that I won't be able to come compete this year.
"It's been a really tough year for me just dealing so much with these shoulder injuries. My doctor insists that I stay home and heal it every single day."
That defeat saw Williams' 186-week reign atop the world rankings end as Germany's Angelique Kerber reached the summit and captured the Flushing Meadows title into the bargain.
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Williams claimed just one Grand Slam title in 2016, at Wimbledon. After that, shoulder troubles hampered her in Rio where her hopes of a fifth Olympic gold medal were crushed in the third round.
Though she begins her next year in Auckland, fans were hoping to see her in Singapore but would be really shocked with her withdrawal.