The hosts scored five tries to two in a dominant performance, notching the biggest win in their rivalry and the second-largest over any New Zealand side.
Fullback Curwin Bosch and second five-eighth Andre Esterhuizen led a compelling display on attack for the Sharks, who also strangled the Highlanders at the breakdown.
The home side held sway at scrum time, exacerbated by a Kings Park turf which broke up badly.
Their fourth win from 10 was comfortably their best and lifts the Sharks just inside the top eight with six games to play.