Always a handful, Manyathela has been somewhat wasteful with the handful of chances that had come his way but he made no mistake when it really mattered after Steve Carr's handball to send the home fans delirious.
It capped an amazing end to a second half that had started to drift somewhat but was brought back to life by Steve Leoelea's free-kick and an own goal to register our leveller just two minutes later.
What the first half lacked in goalscoring opportunities it more than made up for in bite as a few crunching tackles went flying in.
Our best chance came via Matthew Etherington's burst down the left and fine cross straight into the path of Helder Postiga only for the Portugese striker's header to go straight at a grateful Mayala in the Pirates goal.
Jamie Redknapp had a couple of efforts blocked and Chris Perry towered high to meet Etherington's corner but was always struggling to keep his header down.
Pirates, with the support of a frenzied home crowd, built up slowly before exploding into action up front.
Their approach play was impressive but their finishing wayward as Thwala, the lively Manyathela and Makhanya all failed to hit the target.
Defensively we were solid, Anthony Gardner was outstanding and Rob Burch in goal, surely playing in his biggest Spurs game to date, was faultless.
The highlight though was a running battle between Steve Carr and tricky left winger Patrick Thwala. It threatened to boil over at times and was far from friendly, but a joy to watch.
The second half failed to match the first half. Pirates carved out two good chances inside a minute, Manyathela shooting wide from 17 yards and Tshabala also failing to test Burch after Makhanya's dribble and cutback.
Kazu Toda struck a volley at Mayala before the game came to life.
Substitute Lekoelea curled home superbly from 25 yards following a debatable free-kick award after 75 minutes only for us to hit straight bacl when Postiga hit a cross-shot that Musasa could only turn into his own net.
It looked like penalties would be needed to decide the contest until a penalty did just that - Manyathela finally striking the right note from the spot.
MINUTE BY MINUTE GUIDE
10mins: Thwala drive from 25 yards always going wide.
13mins: Free-kick from Manyathela curled a couple of yards over.
16mins: Best chance so far as Manyathela wrestled Perry off the ball and laid the ball back for Makhanya who fired over.
18mins: Redknapp rocket blocked by Mabizela.
21mins: Good feet from Manyathela, tame shot gathered easily by Burch.
22mins: Etherington dart down the left, stood up decent cross met by Postiga but header straight at Mayala.
25mins: Pirates possession sparked into life by skills of Makhanya, Toda great defensive work to shepherd ball out.
38mins: Perry climbed high to meet Redknapp's corner but header always going over.
42mins: Great hands from Burch to pluck out dangerous Tshamala free-kick.
Half-time: Orlando Pirates 0-0 Spurs
49mins: Good build up only for Redknapp to drag shot wide.
53mins: Carr's wicked free-kick somehow missed by both Postiga and Perry.
54mins: Burch our bravely to punch away from Kauleze.
56mins: Best chance so far as Manyathela sliced half-volley a yard wide from just inside the box.
58mins: Another good opportunity for Pirates as Makhanya drove into the box and cut back for Tshabalala who shot wide.
68mins: Toda dipping volley straight at Mayala from 30 yards.
75mins: GOAL. Delightful free-kick into the top corner from 25 yards from substitute Steve Lekoelea. 0-1.
77mins: GOAL. Straight up the other end as Postiga's cross-shot was turned into his own net by Musasa. 1-1.
85mins: GOAL. Carr penalised for handball, Manyathela rammed home from the spot. 1-2.
Starting line-ups: Orlando Pirates: Mayala, Musasa (Dinha, 84), Mabizela, Khomane, Netshodwe, Phakatadi, Tshabalala, Makhanya (Lekoelea, 62), Thwala, Manyathela, Tshamala (Kauleze, 52).
Spurs: Burch, Carr, Taricco (Galbraith, 86), Gardner, Perry, Etherington, Redknapp (Anderton, 80), Toda, Davies, Poyet (Keane, 65), Postiga.
Lesley Manyathela, Pirates top scorer and South African national striker, buried a penalty five minutes from time to clinch Saturday's friendly at a fervent ABSA Stadium in Durban.