Wawrinka and France's Tsonga, who have been at odds in the past, argued heatedly at the first-set changeover and there was no love lost as the Swiss charged to a 7-6 (7/2), 6-4, 6-3 win.
It puts 2014 champion Wawrinka, 31, into his third Melbourne semi-final where he will play the ever-popular Roger Federer, his Swiss compatriot, or Mischa Zverev.
"It's not easy to play against him, he's a strong player," Wawrinka said of Tsonga, adding that barring a big upset he expected to face Federer next.
Earlier Williams' age-defying campaign reached new heights as she beat Russia's Anastasia Pavlyuchenkova to become the oldest woman to reach a Grand Slam semi-final in 23 years.
Williams, 36, won 6-4, 7-6 (7/3) to reach the last four without dropping a set and move towards a possible ninth Grand Slam final against her sister Serena, 16 years after their first.
"Why shouldn't I?" said the seven-time Grand Slam-winner, who is thriving again after a battle with an autoimmune disorder, when asked if she could win her first major title since 2008.
"This mentality is not how champions are made. I'd like to be a champion, in particular this year. The mentality I walk on court with is, 'I deserve this'."
Next up for Williams is her hard-hitting, aggressive fellow American Coco Vandeweghe, who stunned French Open champion Garbine Muguruza to reach her first Grand Slam semi-final.
The tall, powerful Vandeweghe smashed 31 winners past the Spaniard and raced through the second set in just 28 minutes to complete a lopsided 6-4, 6-0 upset win.
"There's more things to do out on a tennis court that I'm hoping to achieve."
Muguruza admitted she had been taken by surprise by Vandeweghe, despite her earlier wins over defending champion Angelique Kerber, Eugenie Bouchard and China's Peng Shuai.
"I was surprised. I think she played unbelievable. Three times we played in the past, she didn't show this level," Muguruza said. "She played very good. Her serve, her shots were there. She barely missed.
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