To compound the Rabbitohs' woes fullback Jye Gray, their best player, left the field with a suspected hamstring injury in the 58th minute and hooker Peter Mamouzelos dislocated his right elbow with one minute to go.
The Knights broke a five-game losing streak at Magic Round on Saturday to get their season heading in the right direction. After scoring 36 points in total in those five matches they were seeking an attacking spark.
Sharpe and Jack Cogger were involved in the good things the side did to give coach Adam O'Brien confidence they are worth persisting with.
Souths are now in the midst of a four-match losing run.
Newcastle skipper Kalyn Ponga, the early favourite to play No.1 for the Maroons in the State of Origin season opener, laid on two tries and started the match full of spark.
The Rabbitohs were already without nine of their top squad, eight due to injury and Latrell Mitchell to suspension.
The way they started suggested they hadn't left the team bus.
The Knights led 18-0 after 14 minutes and appeared set for a mammoth total, before they slipped into old ways with multiple errors.
South Sydney - without halves options Cody Walker, Jamie Humphreys, Jack Wighton and Mitchell - lacked direction.
The kicking games of halves Lewis Dodd, in his first start, and Jayden Sullivan was ineffectual.
Newcastle started with all the running and Ponga laid on a try for Sharpe with a deft left-foot grubber kick.
Sharpe had his second four minutes later when he beat four Rabbitohs from close range with ease, before half Jack Cogger went in.
After the break Ponga sent centre Bradman Best on a bust down the left, supported on the inside and then passed back to Best for a try.
Sharpe did it all himself for his third in a weaving run to the line.
Ponga left the field in the 76th minute after playing with a rib cartilage injury.
