City bounced back from their humbling 4-2 defeat to Adelaide courtesy of O'Neill's long-range strike in the 22nd minute and flick-header in the 88th minute.
Jamie Maclaren had a penalty saved just before halftime while Brisbane's Jay O'Shea equalised from the spot in the 80th minute, before O'Neill salvaged all three points at AAMI Park.
The victory puts premiership-hunting City six points clear of second-placed Adelaide, with a game in hand, while Brisbane sit 11th.
City took the lead when Henry Hore coughed up the ball and O'Neill pounced, charging forward and embarking on a weaving run before fizzing a wonderful strike past Roar goalkeeper Jordan Holmes.
The midfielder has enjoyed a fine season, prompting links to a post-season reunion with Patrick Kisnorbo at Ligue 1 club Troyes, speculation coach Rado Vidosic dismissed during the week.
City came desperately close to a second goal in the 43rd minute when Valon Berisha's curling free kick just bounced off the top of the woodwork.
They should have doubled their lead from the spot four minutes into first-half injury time after Kai Trewin unnecessarily brought Maclaren down.
But the Socceroo's penalty was well-read by Holmes, who made a strong diving save.
A sluggish second half was sparked to life with half an hour to play when Marco Tilio went on a thrilling run and combined with Jordan Bos, who beat a defender and cut back to Berisha, who blasted over the bar.
Brisbane rarely challenged City's defence but received a golden late opportunity to equalise when Callum Talbot unnecessarily clipped Jez Lofthouse just inside the area.
O'Shea stepped up and drove his penalty past Tom Glover.
But City snatched victory when Berisha curled a corner into the mixer and O'Neill rose highest to head the ball home.
Glover denied Nikola Mileusnic at the death to preserve all three points.
20°C