Williams owns a 19-2 record in their WTA Tour matchups and has won 18 in a row, but that lopsided number shouldn't do much to dampen the hype around what will be the marquee match of the opening round at Flushing Meadows, which starts Monday.
Djokovic is the top seed in the men's draw.
Twelve months after losing the final to Naomi Osaka, Williams will have to hit the ground running in her quest for a 24th Grand Slam title.
Among the key story lines that carry over: Williams, who announced earlier this week she would be returning to Auckland for next year's ASB Classic, is trying to equal Margaret Court's mark for most major singles championships.
Their last action on the court was an Australian Open quarter-final where Williams was a comfortable 6-4 6-1 victor in Melbourne in 2016.
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Last year's final ended in acrimony between Williams and chair umpire Carlos Ramos, after he gave her three code violations in the second set.
The final devolved from there and Williams - who then was, and now is, seeking a 24th Grand Slam singles trophy - eventually was docked a point and, later, a game.
In the men's draw, Novak Djokovic, the defending champion and No. 1 seed, had the misfortune of getting Roger Federer on his half of the draw, meaning they could meet in the semifinals.
Top-seeded Osaka opens against Russia's 93rd-ranked Anna Blinkova and could face a third-round date against 15-year-old American Coco Gauff, who eliminated Venus Williams in the first round at Wimbledon in a run to the last 16 in her Grand Slam debut. He is followed by Austrian Dominic Thiem, Russia's Daniil Medvedev and Germany's Alexander Zverev.
Pliskova, who lost her only Grand Slam final to Germany's Angelique Kerber at the 2016 US Open, plays her first match against a qualifier.