"Wow, it's really exciting," Williams said of moving out of a tie with Swiss great Federer for most Grand Slam match wins, AFP reported.
"This is where it all started so it's always so magical out here for me — 308 sounds pretty good."
As Williams, never seriously challenged in a 6-2, 6-3 victory over 52nd-ranked Yaroslava Shvedova, sailed on, one of the two players with a chance to topple her from the world number one spot in this tournament bowed out as fourth-seeded Agnieszka Radwanska was shocked by 18-year-old Croatian Ana Konjuh.
The 6-4, 6-4 triumph avenged a bitter disappointment for Konjuh, who held three match points against Radwanska in the second round at Wimbledon before falling 9-7 in the third round after stepping on a ball and turning her ankle.
"She's an incredible player and I'm just happy to have the opportunity to play her again," Konjuh said. "This time I got the revenge."
The teenager showed remarkable poise throughout the match that closed out the night session on the cavernous Arthur Ashe stadium.
Even when the public address system blared out accidentally as she prepared to serve early in the final game she was not rattled.
"I just said to myself stay in the game don't rush," Konjuh said. "I remember at Wimbledon I had match points there and I thought I'm not going to do that here. I'm not going to let that opportunity go."
Williams will have a day off before tackling Simona Halep after the fifth-seeded Romanian's 6-2, 7-5 victory over Spain's Carla Suarez Navarro.
Despite injury fears sparked by the sore shoulder that hampered her at the Rio Olympics Williams has barely been challenged since arriving at Flushing Meadows, where she claimed the first of her six US Open titles in 1999.
She has reached the business end of the tournament without dropping a set or indeed even dropping her serve. She has faced just one break point in four matches.
A seventh US Open title would take her past the record she shares with Chris Evert, and would also break the Open Era record she shares with Steffi Graf of 22 Grand Slam crowns.
Halep, beaten in seven of eight prior encounters with Williams, was already bracing for the challenge.
"She's like the best player in the world. I don't have to be afraid or to have emotions because I have nothing to lose," Halep said. "It's just a huge challenge for me."
The tantalizing prospect of a semifinal clash between Williams and her sister Venus evaporated as the elder Williams fell to hard-hitting Czech Karolina Pliskova 4-6, 6-4, 7-6 (7/3).
Venus was unable to convert her lone match point as Pliskova, serving at 5-4 in the third, saved herself with a forehand volley then held to extend the match.
With another break under her belt Pliskova had a chance to close it out at 6-5, but after surging to a 40-0 lead she lost five straight points as Venus forced the decider.