Williams is aiming to tie the all-time Grand Slam title record at 24 and move alongside Margaret Court.
While Osaka is looking to become the first Japanese player, male or female, to capture a Grand Slam singles title.
Williams has been in 30 Grand Slam finals but in comparison, Osaka is playing just her first.
Victory for Williams would break her own previous record (2017 Australian Open) by becoming the oldest Grand Slam champion ever.
Williams said: “I couldn’t have predicted this at all. Just been working really hard.
“Like I said, this is just the beginning of my return. I’m still on the way up.
“There’s still much more that I plan on doing. You don’t reach your best a couple months in. That’s kind of where I am now.
“I just feel like there’s a lot of growth to still go in my game. That’s actually the most exciting part.”
Serena Williams vs Naomi Osaka LIVE
First Set (*denotes server)
Williams 0-0 Osaka
20:45: Play is due to get underway at 9pm. In the meantime, read our preview of the final here
20:30: Welcome to LIVE coverage of the US Open final between Serena Williams and Naomi Osaka.