Greens candidate Elizabeth Watson-Brown has likely defeated LNP MP Julian Simmonds in Ryan, in western Brisbane, with more than half the ballots counted on Saturday night.
Ryan has been held by the Nationals, Liberals and LNP for all but one year since 1949.
"We already have transformed the Australian politics, and it's happening in 'Greensland'," Ms Watson-Brown told supporters in her victory speech on Saturday night.
"I could not be prouder, I have never been prouder to be a Queenslander than tonight because we are showing the way.
"We have seen amazing change in the last decades, and change is for the better. Thank you to all of you for that."
Fellow Greens hopeful Max Chandler-Mather is also set to win Griffith, in Brisbane's inner southeast, which was once held by former Labor prime minister Kevin Rudd.
With almost 60 per cent of the vote counted, he's leading LNP candidate Olivia Roberts 62-38, with Labor MP Terri Butler set to lose the seat.
LNP MP Trevor Evans is also set to be unseated in Brisbane, where Labor candidate Madonna Jarrett and Greens hopeful Stephen Bates are set to battle it out with more than half the ballot counted.
Labor's primary vote has also risen marginally with the LNP looking likely to suffer a 5.39 per cent swing against it in a state that helped it cling onto government in 2019.
In all three inner Brisbane seats where the Greens could win, there is a strong representation of young voters and women who care about issues such as climate change.
Labor treasury spokesman and Rankin MP Jim Chalmers said it was disappointing his party hadn't picked up that sentiment in his home state.
"Clearly that aspect of it is disappointing to us because we do have an ambitious, credible climate change policy which is all about cleaner and cheaper energy," he told ABC TV.
Meanwhile, Defence Minister Peter Dutton is likely to hold onto his seat of Dickson in Moreton Bay despite suffering a swing to Labor's Ali France.
The LNP MP was on 53 per cent almost two third of the vote counted in the seat he's held for almost 21 years.
Mr Dutton said it was a "terrible day" for the Liberal Party with a number of his interstate colleagues having potentially lost their seats.
"Now there are still thousands and thousands of postal votes and pre-poll votes to count, so there's some hope and still in some of those seats, but in many of those races it's very tight," he told party faithful.
"So I want to acknowledge the pain that they're going through tonight, their families, their supporters and our supporters across the country."
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