Williams, who was watched by his family at the stand, lost his tight first set before leveling seven in his 23 Grand Slam singles titles at Center Court, the base of seven titles.
He split in the third game, but Dan showed his resilience by fighting back to pick up the thrilling final set at the nail-biting tiebreak.
When asked if this was the final singles match of his long, glorious career, Williams said it was “unanswerable”.
“Who knows where I’ll pop up?” She added.
On Tuesday, a year after retiring from his last first-round match at Wimbledon, he returned to the long-awaited singles division.
During the three-hour, 10-minute meeting the inspiration changed between the two players – the first set was in favor of Don, and then the second set moved towards Williams.
The 40-year-old Williams seemed set to win the deciding set as he served for the win, but there was no memorable return.
Don broke 5-5 and failed to convert a match point to 6-5, but made no mistake when he got a second chance at the tiebreak.
Ranked 115th in the world, Dan played in his first match at Wimbledon Main Draw and his ninth match at all Grand Slams.
“When I saw the draw, I was so scared,” he said after the match. “That’s Serena Williams – she’s a legend. I said, ‘God, how can I play?’ If I win a game or two, it’s very good for me. “
Under the lights of center court, Dan comfortably did more than that – winning against one of the best athletes he had ever seen.
“For my first Wimbledon – wow. Just wow,” she added, struggling to find the words to capture her emotions.
It is unknown at this time what he will do after leaving the post. When asked to summarize his legacy in the competition, he was brief.
“I think I’m very solid on the grass,” he said. “Maybe not today, but it’s pretty solid out there.”
Nadal, SwiTech advanced
Earlier in Tuesday’s matches at Center Court, this year’s French Open champions Rafael Nadal and Iga Swedek won.
Nadal, a two-time Wimbledon winner, defeated Francisco Cerundolo 6-4 6-3 3-6 6-4 in a bid to pursue his 23rd Grand Slam title. Jana Fed 6-0 6-3.
Nadal, who missed last year’s tournament due to injury, received a warm welcome on center court, where he was severely tested by Argentina’s Cerundolo.
The Spaniard was expecting a regular victory 2-0 and had a break in the third set, but Cerundolo, who swung freely, struggled with a double break and won the set.
The match seemed to be heading towards a resolution when the World No. 41 was knocked out in the fourth game, with only Nadal maintaining his best until the last and securing victory with a double break.
Meanwhile, Swedech dominated the first set against Fed in its first game after the French Open, but had to go through a tough period in the second match as the Fed came close to taking a double break.
The first-ranked player recovered from a trembling start to the set, playing five games in a row, increasing his winning streak by 36 matches.