The American won the battle between the world's top two players in one hour and 38 minutes to pick up her 58th career title.
In the men's draw, Roger Federer was chasing a 19th win over home favourite Lleyton Hewitt as the two 32-year-olds renewed their friendly rivalry in today's final. Both players needed three sets to reach the final with top seed Federer beating Frenchman Jeremy Chardy 6-3, 6-7 (3-7), 6-3 and Hewitt overcoming Japan's Kei Nishikori 5-7, 6-4, 6-3 in stifling conditions.
The women's final may have lacked the intensity of Williams' victory over Maria Sharapova on Friday but the crowd did witness a pulsating second set.
The world No 1's serve was far more consistent than in her previous match and she did not face a break point in taking the first set. She was gifted the only break in the seventh game when Azarenka blasted a forehand wide down the line. The American then sealed the set with an ace and an early end to the match seemed likely when she broke the Belarusian in the first game of the second set, but instead it brought her opponent to life. Azarenka broke Williams twice to take a 4-2 lead but lost her own serve to restore parity. In the crucial 11th game, Williams hit a vicious backhand down the line to secure her third break of the set and then served out for victory.
Azarenka, who split four matches with Williams last year, was not too disappointed, saying after the match: "I hope to meet you in Melbourne."
Williams believed the week in Brisbane was the perfect preparation for Melbourne and is also eyeing another meeting between the pair.
"I feel like I'm being pushed into the deep end straight away," she said. "I think it's a good thing. In Melbourne if I have to face Maria again I'll know a little bit more what to expect, and the same with Victoria. I hope we do play in Melbourne too because that would mean we'd be going the farthest."
Conditions were far easier for the women finalists than for the first men's semi-final between Hewitt and Nishikori, where both players struggled as the temperature reached 42 degrees.
"When you just come off the court it feels like it's the worst you've played in," said Hewitt, who will be playing his first ATP Tour final on home soil for eight years. "It was a really heavy humidity feel out there. I was sweating just walking out to have my warm-up."
The Australian has won just eight of his 26 matches with Federer but came out on top in their last meeting in the Gerry Weber Open final four years ago and is looking forward to another chance to improve his record.
"You want to play against the best players," Hewitt said. "Obviously Roger and I have a good history and a lot of tough matches in the past in slams and Davis Cups and everything. I'm going to enjoy it."
Federer was far from at his best against Chardy, losing the second set in a tie-break. However, as his opponent's serve fell apart in the third set, Federer swooped.
"Jeremy has a great serve and made it tough for me," said Federer. "It will be very different against Lleyton. He has the game to cause me a lot of problems. It's always special when we play."
While Serena was winning in Australia, sister Venus was losing her final in New Zealand, going down to Ana Ivanovic 6-2, 5-7, 6-4 in the Auckland Classic. The 26-year-old Serb had not won a title since she completed a 6-3, 6-0 victory over Spain's Anabel Medina Garrigues in Bali at the end of 2011.
At the Shenzhen Open, Li Na edged out compatriot Peng Shuai 6-4, 7-5 to defend her title in the second all-Chinese final on the WTA tour.