Such has been the 31-year-old's dominance that watching how her compatriots, even sister Venus these days, fare at Grand Slams has been rendered academic.
On Tuesday, however, 18-year-old Madison Keys underlined that the former powerhouse nation has plenty in reserve.
Just before Williams polished off Mandy Minella to begin her tilt at a sixth Wimbledon crown and a 17th major singles title, teenager Keys marked her debut at the grasscourt slam by beating British hopeful Heather Watson.
With 20-year-old Sloane Stephens ranked 17, Jamie Hampton, who she beat on Monday at 25, Bethanie Mattek-Sands ranked 58 and Christina McHale and Mallory Burdette also just inside the top 70, progress is clearly being made.
"I think it's great. I think for the past 12 months we've seen a lot of growth in American tennis," Williams said after marching into the second round.
"A couple of years ago when I was asked that question, I wasn't sure of the answer. But now I can answer that in so many different ways. There's so many great young American players.
"I know at the French Open we had the most people in the draw than any other country. So that's really a huge step."
There is greater concern about the health of the American men's game which has lacked a Pied Piper since former world No.1 Andy Roddick retired last year.
Sam Querrey is currently the highest American man in the ATP rankings at 19th and he lost in the opening round of Wimbledon against Australian Bernard Tomic on Tuesday.
John Isner is not far behind but others, such as Ryan Harrison and Jack Sock, are yet to fulfil their potential.
With Serena showing every sign of surpassing fellow Americans Martina Navratilova's and Chris Evert's 18 Grand Slam singles titles, the likes of Stephens and Keys can continue to thrive in her shadow, ready for when she calls it a day.
Evert, working at Wimbledon for broadcaster ESPN, has no doubt someone will step up when Serena is no longer putting fear into her opponents and is excited about Keys.
"Madison definitely has the weapons to be top five. She has the weapons to be number one," Evert said.
"There's so much more that goes into it than physical weapons. I can say she almost matches Serena's serve as far as power. Out of all the players out there, she comes the closest to Serena's serve. The power off both sides is tremendous.
"What remains to be seen is the mental side of the game, which really hasn't been tested as much because she is an up-and-coming player and she has no pressure.
"But of all the young players, I would have to say she, even more than Sloane Stephens, has the potential to be top 10."
Keys showed admirable composure on Tuesday, coping with the nerves of playing a home favourite to take the opening set off Watson in style and then battling back to win the second.
The Florida-based player, who once beat Serena 5-1 in a World Team Tennis event, aged 14, said the support provided by the United States Tennis Association was paying dividends.
"I just really love that being in different countries, you know, we still have a support group, and there's people to be around," she said. "I think it would be very hard if there were just one or two of us the entire time we were here."
Triple Wimbledon champion John McEnroe acknowledges that the American men's scene is more threadbare than the women's with no player looking like becoming the country's first major winner since Roddick's 2003 U.S. Open title.
"Sam Querrey has been a solid professional, John Isner got to 10 in the world. Mardy Fish got to the top 10 before it overwhelmed him," he said in an ESPN conference call.
"The athleticism necessary is becoming even more exceptional. That's something we have to try to search out and provide the opportunity for kids that don't have it.
"I believe (American) girls are much more likely to play tennis than boys. The greatest American athletes played football or basketball. We're lower down on the totem pole."
- Sports & Recreation
- Madison Keys
- Sloane Stephens
- Chris Evert
- Sam Querrey