"Wow. That's pretty awesome and honestly what a better place to do it than here, where it all started," Williams told an adoring Arthur Ashe Stadium crowd.
"It is actually a really good feeling. To be up there with both men and women is something that's super rare."
Serena delighted by with milestone win
Serena was in total control throughout, and won the last 14 consecutive points as she dismissed her opponent.
"I knew it was on the horizon," Williams said of the record.
"I knew at Wimbledon that I wanted to get there. Obviously I'm excited about that. I would like to take one more step, several more steps."
Now that's how you hit a drop shot - stunning from Serena
Among the highlights was a picture-perfect drop shot hit from behind the baseline, while the usual Williams combination of power and precision was in full effect.
Larsson hits double fault way, way, waaaayyy wide
Larsson fought admirably but could never live with her record-breaking opponent, who said on court afterwards: "I'm female and I'm an athlete. And I'm an athlete first."
It was at Flushing Meadows where Williams won her first grand slam in 1999 and 17 years later it is where she could achieve two more career landmarks if she can reach the winner's circle again on September 10.
A record seventh US Open title would give Williams 23 career grand slams, moving her past Steffi Graf again for the most in the Open Era, and just one shy of Margaret Court who tops the all-time list with 24.