Cale struck at the death after Ayanda 'Cobra' Dlamini netted a 85th minute opener for Usuthu at Cape Town Stadium.
The result leaves Ajax fourth on the Absa Premiership table with 24 points from 17 games - 19 points adrift of runaway leaders Kaizer Chiefs.
AmaZulu remain bottom of the standings with nine points from five matches - six points shy of escaping the drop zone.
Steve Barker's side came to Cape Town after a 1-1 draw with KZN rivals Maritzburg United, while Ajax had just lost 4-0 to Orlando Pirates.
The home side also had a few injury problems ahead of the game with Nathan Paulse, Keagan Dolly, Abubbakar Mobara and Dominic Isaacs all unavailable.
But Ajax began well and took the game to Usuthu who started with a 5-4-1 system with ex-Ajax man Nhlanhla Shabalala playing a deep defensive midfield role.
Ajax thought they had found the opener when some clumsy AmaZulu defending saw Ajax awarded a penalty, but Cale’s kick was saved by Aubrey Mathibe.
AmaZulu had a good chance in the 36th minute when Philani Shange got into space down the right wing, but his final pass was not good enough and the opportunity was missed.
But Barker’s unit should have taken the lead in the 39th minute when Bongani Ndulula missed from close range at the far post when he had got onto the end of a delightful cross.
Thirteen minutes into the second half and AmaZulu substitute Tshepo Liphoko began to show his intent when he fired a shot over the bar after combining with Goodman Dlamini.
But what followed was a strong reply from the home side in the 59th minute. First Mathibe tipped a powerful shot from Cale over the bar. Then he saved from close range to deny Tashreeq Morris a few seconds later.
Then in the 65th minute Cale ran onto a through pass and on the turn he shot at goal with his weaker right foot, only for the ball to drift wide of target.
AmaZulu came close to scoring once again in the 73rd minute when A. Dlamini got into a good position but he took his time and missed the opportunity to punish the Ajax defence.
AmaZulu then found the net through Cobra in the 86th minute following a goal-mouth scramble, but Ajax replied through Cale, who struck a venomous shot past Mathibe after a free-kick was played short to him.