The 800m world champion won the 1 500m in 4 minutes, 22.64 seconds and then clocked 53.18 seconds in the 400m final in Stellenbosch, the town where she was prevented from competing a year ago in the midst of her gender dispute.
Representing the University of Pretoria, the 20-year-old Semenya was nearly 10 seconds slower on Friday than the 4:12.93 she ran to win the 1 500m at the South African nationals this month.
In March last year, Semenya was blocked from running at a meet in Stellenbosch, near Cape Town, while the IAAF reviewed the results of gender tests she underwent at the 2009 world championships. She was cleared to run by the world athletics body in July.
Semenya is strongly favored for a third gold at South Africa's national student championships on Saturday in her favored 800m event. She will then head overseas next month to prepare for the defense of her 800m title at this year's world championships in Daegu, South Korea, which begin in August.
Semenya is scheduled to continue her build up to the worlds at the IAAF World Challenge in Dakar, Senegal, on May 28 before running in her first Diamond League meet of the season at the Prefontaine Classic in Eugene, Oregon on June 4.