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Semenya, a two-lap specialist, used her endurance to her advantage as she got her season off to an impressive start.
The former world 800m champion made her charge in the final 120m and passed a tiring Justine Palframan who had set a fast pace from the gun.
Despite a heavy head wind, at times measuring up to five metres per second, Semenya's power was evident as she strode past the flagging Palframan who was second in 54.00.
Thuso Mpuang of the Free State won the men's short sprint double, crossing the line first in both the 100m and 200m by narrow margins.
Mapaseka Makhanya also doubled up, winning the women's 800m, in the absence of Semenya, and 1 500m races.
The distance runners were hampered by the wind, with Pieter van der Westhuizen clocking 3:41.74 to win the men's 1 500m, falling more than three seconds short of his goal -- the 3:38.00 Olympic qualifying standard.
Gauteng North teammates Stephen Mokoka and Gladwin Mzazi, and Elroy Gelant of Central North West, also fell short in their effort to meet the men's 5 000m standard of 13:20.00.
Mzazi secured a surprise victory in 13:28.25, with Mokoka edged into second.
Gelant, who will compete over 3 000m at the World Indoor Championships in Istanbul next week, was a distant third, nearly 18 seconds off the pace.
