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South African Fanie Matshipa, who had done a lot of the hard work, pushing the pace in the second half, held on to finish second.
Russian Elena Nurgalieva, the defending champion, recovered from an early fall to win her sixth title in the women's race ahead of twin sister Olesya.
Muzhingi's countryman, Point Chaza, had broken away early and held a lead of more than seven minutes at the halfway mark, which he crossed in 2:36.19, on record pace.
Chaza, however, faded soon after with Muzhingi and Matshipa storming past with 30km to go.
Matshipa looked to be in control, but Muzhingi's experience showed and he stole clear with 14km remaining to win the 87km ultra-marathon in 5:32.45.
Muzhingi, who won the 'down' run the last two years, secured his maiden victory in the 'up' run to become the first athlete to win three titles in succession since Bruce Fordyce bagged his eighth straight win in 1988.
Matshipa, who was fifth last year, struggled over Polly Shortts, the last of the race's five big hills, but held on to cross the line in 5:34.29.
Another South African, Claude Moshiywa, who had faded to seventh last year after taking the early lead, ran a much wiser race to finish third in 5:42.05, holding off Jonas Buud of Sweden by 39 seconds.
The Nurgalieva twins took the lead from the start, and while Elena took a tumble 27km into the race, she recovered quickly to catch her sister and they gradually stretched the gap over South African Farwa Mentoor.
Elena broke away in the dying stages to win in 6:24.11 - the slowest winning time in the women's race since 1999 - and Olesya finished in second position, 14 seconds behind her sibling.
Mentoor, the first South African woman to finish, struggled in the last third of the race, and was passed by American Kami Semick and Ellie Greenwood of Great Britain, but held on to take fifth place in 6:35.49.
South African runners filled seven of the top 10 positions in the men's race, and four of the top 10 places in the women's category.
Top men's results:
1 Stephen Muzhingi (ZIM) 5:32.45,
2 Fanie Matshipa (RSA) 5:34.29,
3 Claude Moshiywa (RSA) 5:42.05,
4 Jonas Buud (SWE) 5:42.44,
5 Gift Kelehe (RSA) 5:43.59,
6 Chasara Masiyatsva (ZIM) 5:44.33,
7 Ludwick Mamobolo (RSA) 5:50.17,
8 Charles Tjiane (RSA)5:50.46,
9 Brian Zondi (RSA), 5:51.08,
10 Mncedisi Mkhize (RSA) 5:51.17
Top women's results:
1 Elena Nurgalieva (RUS) 6:24.11,
2 Olesya Nurgalieva (RUS) 6:24.35,
3 Kami Semick 6:26.24 (US),
4 Ellie Greenwood (GBR) 6:32.46,
5 Farwa Mentoor (RSA) 6:35.49,
6 Irina Vishnevskaya (RUS) 6:42.07,
7 Elizabeth Hawker (GBR) 6:48.28,
8 Adinda Kruger (RSA) 6:49.01,
9 Kerry Koen (RSA) 6:56.20,
10 Riana van Niekerk (RSA) 6:56.38
