The victory completed a remarkable run of domination by the No. 4-seeded Williams, who lost only 17 games in six matches en route to her first singles gold medal. She went 13-0 this summer at the All England Club, where she won her fifth Wimbledon title a month ago.
"I was so focused here," she said. "I remember I was serving and I was thinking: 'Serena, this is your best chance to win a gold medal. You're at Wimbledon, you're on grass, you play great on grass, pull it together, just win this.' And that's what I thought about."
The career Golden Slam was first achieved by Steffi Graf, who did it when she won at the Olympics in 1988 after sweeping all four major titles. Williams can add the gold medal to her 14 Grand Slam singles championships, the most of any active woman.
And she's not done in London. Williams and her sister Venus, pursuing their third gold in doubles, beat Maria Kirilenko and Nadia Petrova of Russia 7-5, 6-4 in the semifinals. Their opponents Sunday will be Andrea Hlavackova and Lucie Hradecka of the Czech Republic.
It took the No. 3-seeded Sharapova 45 minutes to win a game, and by then she trailed 6-0, 3-0. Williams dominated with her serve and repeatedly blasted winners from the baseline, taking a big swing with almost every stroke despite gusty conditions on Centre Court.
The wind was so strong it blew the U.S. flag off its pole during the medal ceremony.
When Sharapova wasn't lunging or whiffing as the ball whizzed past, she was caught off-balance trying to block back shots at her feet. Williams finished with 10 aces, 24 winners and only seven unforced errors.
"She's playing incredibly confident tennis," Sharapova said. "Her shots were very powerful."
Sharapova completed a career Grand Slam in June by winning the French Open, but Williams beat her for the eighth consecutive time. The most one-sided previous women's final was in 1920, when France's Suzanne Lenglen beat Dorothy Holman of Great Britain, 6-3, 6-0.
Top-seeded Victoria Azarenka of Belarus won the bronze by beating No. 14-seeded Maria Kirilenko of Russia 6-3, 6-4. Sharapova's loss allowed Azarenka to retain the No. 1 ranking.
Roger Federer will try to complete a career Golden Slam when he plays Andy Murray of Britain in the men's final Sunday.
Williams took charge of the final from the start, sweeping the first eight points. The crowd wanted to see a contest and saved its biggest cheers for the rare occasions when Sharapova won a point.
There was no giving up by the Russian, one of the most dogged players on the women's tour, but there was no letup from Williams. When she ripped a return winner for a 2-0 lead in the second set, she screamed "Come on!" as if trying to jump-start her game.
She had a similar outburst two games later after whacking a winner to erase a break point, one of only two she faced. She was broken just once in the tournament.
At 15-15 in the final game, a spectator shouted, "Don't give up, Maria."
One point later someone else hollered, "Maria, I still want to marry you."
When Williams closed out the victory with her 60th ace of the tournament, she let out a long scream. After shaking hands with Sharapova, Williams hopped a dozen times on the grass she loves, waved and then hopped some more.