There were A-League wins for Western Sydney Wanderers and Melbourne City, while Perth Glory held Brisbane Roar to a draw
Brendon Santalab scored the decisive goal as Western Sydney Wanderers ended Sydney FC's unbeaten run and claimed their first derby win in over three years.
The striker found the net in the 26th minute with a right-footed shot from the centre of the box after being set up by Mitch Nicols to give the hosts the lead, and Western Sydney went on to win 1-0.
Leaders Sydney had a number of chances to restore parity, with Bobo and Milos Ninkovic in particular threatening on more than one occasion, but Vedran Janjetovic - up against his former club - proved to be too much of an obstacle between the sticks.
The loss ends the Sky Blues' tilt at an undefeated season, with Sydney having publicly declared they wanted to become the A-League's first 'Invincibles' side a number of times in this campaign.
The result also ended the Wanderers' drought in the Sydney derby, with Tony Popovic's side claiming victory for the first time in 10 fixtures against their local rivals.
Sydney remain top of the table despite Saturday's defeat, 11 points clear of Melbourne Victory, who meet Central Coast Mariners on Sunday.
Western Sydney sit sixth in the table and now hold a three-point lead over Newcastle Jets in the race for a finals place.
Elsewhere, Melbourne City thrashed Wellington Phoenix 5-1 to move to end their three-game winless streak.
Kosta Barbarouses missed an early spot kick for Wellington, before an own goal from Ryan Lowry and a Bruno Fornaroli strike handed Melbourne a two-goal lead at half-time.
Anthony Caceres made it three on the hour mark before Barbarouses pulled one back for the home side with 20 minutes left on the clock.
There would not be a miraculous comeback, though, as Neil Kilkenny and Nicolas Colazo piled even more misery on the hosts in the closing stages.
Brisbane Roar had to settle for a 2-2 draw at Perth Glory as they dropped to fourth place in the table.
The visitors twice took the lead through Jamie Maclaren and Dane Ingham, but goals from Nebojsa Marinkovic and Adam Taggart ensured a share of the spoils for Perth.