The Roar soared to a three-goal buffer on Saturday before the Sky Blues mounted a serious challenge in the final 20 minutes of regulation time.
Tiago Quintal came off the Sydney bench and struck in the 84th minute before fellow substitute Jordan Courtney-Perkins closed the gap further four minutes later.
The hosts were given seven minutes to salvage a point but it was a desperate Roar outfit that prevailed.
It is the last-placed Brisbane's first win since April 2024 and will be much cherished for the owners of the worst record from the first 12 games of a season in the 20-year history of the competition.
"(This is) one of the toughest periods that you can probably have as a club," Roar coach Ruben Zadkovich said.
"To see the way that they stick together and the way that they keep continuing working hard for each other every day, I'm just really proud that they got their just rewards tonight."
Sydney blew their chances to move into the top two and have now dropped two places to sixth, picking up only one point in their last two matches after a goalless mid-week draw with Wellington.
They could drop to seventh if Melbourne Victory beat Adelaide United later on Saturday.
"We weren't at the races today," Sydney coach Ufuk Talay said.
"From the get-go, I thought we were very lethargic and very slow.
"We finished the game strong, but the game was gone by the time we started to push for it."
It took just one long kick down the middle from captain Jay O'Shea to open the floodgates.
O'Shea sent the ball flying down the middle and over the heads of three Sky Blues defenders to teammate Ben Halloran.
Halloran tapped the ball over goalkeeper Harrison Devenish-Meares with incredible ease to open the scoring in the 15th minute.
Roar lead after 15 minutes �— Paramount+ Australia (@ParamountPlusAU) One long ball undoes the Sydney defence and Ben Halloran finishes with classWatch #SYDvBRI now on Paramount+ 📺 pic.twitter.com/wAljMXmuxdJanuary 18, 2025
O'Shea notched another assist five minutes later with a clinical slice through a congested penalty area to help Henry Hore announce his return from a loan spell at K League club Gangwon FC in style.
Sydney pulled one back via Joel King in the 31st minute but it was a minor hiccup for the visitors, with Adam Zimarino restoring the two-goal buffer nine minutes later.
Brisbane looked to have settled the matter in the 71st minute after a precise volley from 17-year-old Lucas Herrington before the hosts came to life late.
Sydney will be without Anthony Caceres for at least one game through concussion after the midfielder clashed heads with Samuel Klein in an attempt to clear an airborne ball in the 58th minute.
While Klein was able to see out the match, Caceres was visibly dazed and needed patching up for a gash on his head.
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