On Monday evening, however, Frances Tiafoe (24) continued another unlikely tale of success against the odds with a magical display to knock out Rafa Nadal (36) on the same Arthur Ashe Stadium court where Serena waved an emotional farewell.
While Serena and older sibling Venus's rise from the public courts of Compton in Los Angeles to become world number ones and in Serena's case, the greatest of all time, is part of tennis folklore, Tiafoe's journey is still unfolding.
After crushing Nadal in four sets to reach the quarter-finals of his home Grand Slam for the first time, the 24-year-old turned to salute his parents sitting up in the stands. And no wonder.
His father, Frances Snr, and mother Alphina Kamara fled the civil war in Sierra Leone and eventually settled in Maryland where Frances Snr worked as a labourer with a construction firm building a new tennis centre.
After it was completed, he was offered a job as an on-site caretaker at the Junior Tennis Champions Center in College Park and it was there that his twin sons Frances and Franklin regularly stayed the night, getting to hit balls on the courts.
By the time he was five, Frances was already displaying the ball-striking skills and athleticism that captivated the crowd on Arthur Ashe on Monday as Tiafoe earned the biggest win of his career to set up a clash with Andrey Rublev (24).
Tiafoe, whose mum worked nights as a nurse, spent most of his young life at the tennis centre and in 2013, aged 15, won the prestigious Orange Bowl and began being touted as the next big thing in American tennis.
Unlike the Williams sisters, who he watched in awe as a child, Tiafoe's move into the professional ranks was not quite as spectacular and it took him a while to adjust.
A quarter-final run at the 2019 Australian Open, where he lost to Nadal, was his breakthrough at the Slams but it is only in the last couple of years that Tiafoe has found the consistency to regularly knock over the big names.
After beating Nadal, he recalled the early days watching the Williams sisters and realising what was possible for a young African American player with big dreams.
"Watching Serena and Venus play finals of Grand Slams at that time, when I was super young. I was like, how cool would it be to play Wimbledon, to play on Arthur Ashe and stuff like that," Tiafoe told reporters. "I just had a big passion for the game. Not even mainly for me, but to do it for (my parents)."
Fourth-round runs at the US Open in 2020 and 2021 have now been surpassed and Tiafoe is in no mood to stop now, especially with A-list support coming in from his sporting idols such as NBA great LeBron James (37).
"Man, I was losing it in the locker room. Bro, I was going crazy," he said about receiving a Twitter message from LeBron which read: "CONGRATS Young King!!!".
Tiafoe said his heart was beating at '1,000mph' when he shook hands with 22-time Grand Slam champion Nadal and he anticipates another wild night when he faces Rublev on Wednesday.
"Yeah, Slams, crazy things can happen," the 22nd seed, bidding to become the first American man to win the US Open since Andy Roddick (40) in 2003, said.
"Especially here in New York. It's going to be a fun ride."
