Williams was overwhelmed with emotion after being forced to dig deep to dispatch the spirited Aravane Rezai of France 6-3 3-6 6-1 on Centre Court.
The 29-year-old Wimbledon champion was playing only her second tournament since recovering from surgery undertaken in March to remove life-threatening blood clots in her lungs.
By her own admission she was "on my death bed at one point - quite literally", and her ability to continue playing at the highest level has been questioned.
But Williams dispelled any lingering doubts by coming through a precarious second set to crush a determined opponent playing aggressive tennis.
Upon completing her victory the four-time Wimbledon winner began crying and later credited her fighting spirit for leading her though troubled times.
"It definitely hit me at the end of the match. I usually don't cry," she said.
"It was definitely emotional for me because throughout the last 12 months I've been through a lot of things that aren't normal, that people don't even know about.
"It's been a disaster year and a long, arduous road. To stand up still is pretty awesome.
"I just wanted to win at least one match here and since I'm not playing doubles it was a really big win for me.
"To be able to come back at Wimbledon is pretty awesome, I didn't expect to play so I'm just really excited.
"This was probably the most emotional I've been after a match. For me it wasn't about winning the match, it was about being out there.
"Everyone that has had some troubles, whether it be health or something else, later you realise that you can do it.
‘‘You must have faith. You must believe in yourself, continue to fight and never give up. I always preach never give up, never, never give up.
"It just really goes to show if you don't give up, you still have a chance."
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