Canterbury Bulldogs secured their first win over South Sydney Rabbitohs since April 2014 at Stadium Australia, with the champions' outing worsened by a late injury to skipper Greg Inglis.

The Rabbitohs had racked up a three-match winning streak over their opponents, which included a 30-6 success in last year's Grand Final, prior to Friday's encounter.

And the designated away side were forced to hold off a late Rabbitohs fightback, having eased into a 22-0 lead by the interval.

Damien Cook got Bulldogs off to a strong start, going over 10 minutes in, before Trent Hodkinson's lofted delivery found Sam Perrett for a second soon after.

Hodkinson made it two from two with the boot, Brett Morris and Perrett adding further tries before the interval for a dominant lead.

The Rabbitohs sought to keep their top-four hopes in rude health as Bryson Goodwin, Alex Johnston and Jason Clark all went over, with Reynolds adding the extras.

However, the Bulldogs found the line with regularity, Curtis Rona crossing before the hour, while Shaun Lane also broke up the hosts' momentum with a try of his own 12 minutes from time.

A difficult evening for the Rabbitohs was made worse when Inglis limped off after requiring lengthy attention for his strapped right knee as the Bulldogs moved within two points of their fourth-placed opponents.