Nel-Peters, a 22-year-old business management graduate, beat out 91 other candidates during the finals held in Las Vegas. South Africa last won Miss Universe in 1978.
She succeeded France's Iris Mittenaere, who was crowned in Manila last January.
Colombia's Laura Gonzalez placed first runner-up, Jamaica's Davina Bennett was second runner-up. The Philippines' Rachel Peters finished in the Top 10.