Madsen is seeking his second consecutive victory on the European Tour, having won for the first time last week at the South African Open.
He suffered a lone bogey at the Leopard Creek Country Club, that coming at the par-3 seventh, and finished the round with three birdies in his final four holes.
Allan Versfeld and Ricardo Santos were tied for second at 66. Defending champion and former Masters winner Charl Schwartzel turned in a 68 and shared fourth with Victor Riu, Richard Finch and David Drysdale.
Swim Week Miami Beach 2014 [PHOTOS]