Eric Tinkler was taking charge of Sekhkhune for just the third time in the league since being sacked by City, and recorded his second win, after a 2-1 victory over Marumo Gallants and 2-1 defeat to Stellenbosch - alongside a 1-0 Nedbank Cup quarter-final loss to Mamelodi Sundowns.
Samkele Sihlali opened the scoring at the Cape Town Stadium after 27 minutes before Chibuike Ohizu doubled his side's lead with 42 minutes on the clock.
Khulekani Shezi was then dismissed on 46 minutes and Kayden Francis netted for the Citizens on 76 minutes, but Babina Noko held on for the win.
The result saw Sekhukhune move into third place with 37 points from 23 games and left an Andre Arendse-led City down in 14th place with 24 points from 25 games.
Tinkler's side had started on the front foot and were soon in the lead when Sihlali made the most of some ineffective defending to sneak in for the lead.
Amadou Soukouna came close to levelling with a shot from outside the box, but he was unable to keep his effort on target.
And the miss was to prove crucial as Ohizu doubled Sekhukhune's advantage with a tap in from a Vuyo Letlapa pass.
The second half had barely started when Shezi received his marching orders for a rough challenge.
It took time for City to make use of the extra man, but second half substitute Francis found himself well placed with just over 20 minutes of the match remaining to slot home a Jaedin Rhodes delivery.
Sekhukhune were determined to see out the result and even had a good chance to extend their lead late on through Letlapa, but he snapped at the shot and fired wide.
City though were unable to find a way back into the game and ultimately suffered their 13th loss of a massively disappointing campaign.