Goal kicking proved to be the difference with both sides scoring four tries-a-piece, with halfback Christian Hazard collecting a double.
The Rabbitohs opened the scoring in the third minute through Hazard, following two good offloads from prop Daniel Smith and winger Alex Johnston.
The Broncos struck back straight away, scoring in the sixth minute of play through second rower Caleb Timu. Ashley Taylor converted giving the home side a 6-4 advantage.
Six minutes later the Rabbitohs scored their second try, with fullback Tyrone Phillips dancing through the defensive line to score to the left of the posts. Will Paterson converted, establishing a four-point buffer for South Sydney.
Hazard's short kicking game was very strong, keeping the Broncos under pressure and earning repeat set-on-repeat set.
He was rewarded with his second try for the match in the 26th minute when he sliced through to score out wide on the left, taking the lead to 14-6.
Timu scored his second try for the Broncos in the 38th minute, taking on the winger with his size to score in the right hand corner. The conversion was unsuccessful and the Rabbitohs led at the break, 14 points to 10.
Broncos prop Ben Garcia was the first to score in the second half with a strong charge to the line in the 49th minute, with Taylor's conversion giving the Broncosa two-point lead.
The Broncos scored again in the 62nd minute when fullback Kurt Capewell chased through a grubber kick to score on the right. Taylor converted to extend the lead for the home side to eight points.
The Rabbitohs hit back 15 minutes before full time when winger Alex Johnston made the most of a long break from Phillips, scoring to the right of the posts. Paterson converted, reducing the deficit to just two points.
The Rabbitohs tried hard to break the Broncos' line again over the final stages of the match, and had their best opportunity to score with a minute left in the match, but the final grubber kick trickled long and the Rabbitohs had gone down in a thriller, 22 points to 20.
Brisbane Broncos 22(Caleb Timu 2, Ben Garcia, Kurt Capewell tries; Ashley Taylor 3 goals)
South Sydney Rabbitohs 20 (Christian Hazard 2, Tyrone Phillips, Alex Johnston tries; Will Paterson 2 goals)