Biles' impressive Yurchenko double pike, a vault so difficult that it has never been performed by another female gymnast, was the highlight of the night as she led Shilese Jones by 2.55 points overall at the halfway point of the two-day event.
The four-time Olympic champion posted the highest scores in three of the four apparatus - vault (15.700), floor (14.800) and beam (14.450). Her 14.350 on the uneven bars was third behind Jones (14.900) and Skye Blakely (14.400).
Biles thrilled a sold-out crowd at the US Classic earlier this month, making a triumphant return from the COVID-delayed Tokyo Games two years ago, when she had pulled out of multiple events due to the "twisties", a temporary loss of air awareness.
She can become the first gymnast to win eight US all-round titles, breaking the record set by Alfred Jochim in 1933 and matched by Biles in 2021.
Biles would also be the oldest woman to win the championships if she can back up her dazzling display when the women's competition concludes on Sunday.
"I think beam started off a little bit rough, but that's kind of to be expected," Biles told broadcaster NBC. "You get your nerves out of the way and then after that it was pretty smooth sailing. I'm pretty happy with the overall meet today."
Jones, the runner-up at the nationals last year and a three-time world silver medallist in 2022, posted 56.550 points overall, with Blakely third at 55.700.
Leanne Wong, who finished runner-up to Biles at the US Classic, was in fourth place at 55.350 and 2020 Olympic silver medalist Jordan Chiles was in fifth (54.600).
Reigning Olympic champion Sunisa Lee had also returned to elite gymnastics at the US Classic and competed only on vault and balance beam on Friday, as she continues to battle a kidney ailment that has limited her training and cut short her college career.
Biles and Lee headlined a stellar field at the event, which marked the first time that two Olympic all-around gold medallists have competed in the same U.S. championships.
As was the case in suburban Chicago three weeks ago, the "twisties" were nowhere in sight as Biles took another step towards competing at this year's world championships and her third Olympic Games in Paris next year.
Eight gymnasts from the US nationals, including the top two finishers, will be invited to a U.S. camp next month, after which a five-woman team will be selected for the worlds, which begin on Sept. 30 in Antwerp, Belgium.