The left-hander led the visitors to 207-3 from their 20 overs with a magnificent knock that took only 55 balls and combined power hitting and finesse.
Reeza Hendricks, who opened the innings for Rossouw and shared a partnership of 72 for the second wicket, followed up his 50 in the first T20 with a stunning 53 off only 32 deliveries.
The loss of captain Jos Buttler and Dawid Malan early in the powerplay hurt England’s response, and Jason Roy’s problems persisted as the hosts fell to a score of 77-3.
The fielding of South Africa was sloppy on Wednesday in Bristol, but Keshav Maharaj took a sensational diving catch on the boundary to eliminate Moeen Ali.
Jonny Bairstow was taken out of the game by another excellent catch by Lungi Ngidi, ending England’s aspirations.
England was bowled out for 149 with more than three overs left, Andile Phehlukwayo and Tabraiz Shamsi were the outstanding bowlers, each taking 3-27.
On Sunday, the pivotal T20 will occur at Southampton’s Ageas Bowl.