CAF Champions League contenders Mamelodi Sundowns and Orlando Pirates suffered shock Nedbank Cup round-of-32 losses Saturday along with trophy-holders Free State Stars.
Burundian Frederic Nsabiyumva outjumped four Sundowns defenders and the goalkeeper to nod a stoppage-time winner as Chippa United upset Sundowns 2-1 in Port Elizabeth.
Pirates suffered more penalty pain as they lost a shootout 5-4 after drawing 1-1 against Black Leopards in Thohoyandou after extra time.
Free State crashed at the first hurdle in defence of the title as they slumped 2-1 at home to second division outfit Richards Bay in Bethlehem.
Cape Town City, Golden Arrows and second-tier TS Galaxy were other winners in the richest national cup in Africa with a seven million rand first prize.
"The people of Port Elizabeth can walk with pride again," said Chippa coach Clinton Larsen after his second successive win since joining a club struggling for top-flight survival.
"It is nice to get that winning feeling back," he added after becoming the fourth coach this season of Chippa.
Rhulani Manzini had Chippa in front after only three minutes, Phakamani Mahlambi levelled before half-time and Nsabiyumva deserted his centre-back role to score the match-winner.
Pirates have not won a domestic shootout since 2014 and the curse continued before a 20,000 crowd.
Meanwhile mid-table second division outfit Richards Bay rattled lethargic Free State by scoring twice in the second half through Michael Gumede and Siyanda Ngubo.
Sifiso Mbhele raised hopes of a dramatic comeback by the trophy-holders by firing into the net from close range with 11 minutes remaining, but the visitors survived.
Hosts Cape Town brushed aside disappointing SuperSport United 2-0 in an all-Premiership showdown through goals from Thato Mokeke and Thamsanqa Mkhize.
The match was a repeat of the final of a competition reserved for the top eight finishers in the previous league season and won by Cape Town on penalties.
Arrows stretched to four matches in all competitions an unbeaten run under new coach Steve Komphela by outclassing lower-league side Tjakastad Junior Shephard 3-0 in Nelspruit.
