The men in green and gold saw all their good work from a brilliant first-half performance undone as they were overrun by South American opposition
Australia held a comfortable advantage thanks to Mile Jedinak's penalty and a brace from Tim Cahill, who, playing at his old Millwall stomping ground, broke Damian Mori's record to become the national team's all-time leading goal-scorer.
Ecuador came out after the break looking more like the team which finished fourth in CONMEBOL World Cup qualifying, laying siege to the Socceroos' goal and forcing a series of mistakes on their way to registering an unlikely comeback victory.
Postecoglou made five changes from the team which beat Costa Rica 1-0 in his first friendly in charge in November. With Lucas Neill not picked and Rhys Williams injured, Matthew Spiranovic and Curtis Good were chosen at centre-back, the latter making his international debut.
Mark Bresciano, Dario Vidosic and another long-term injury victim, Robbie Kruse, were all absent from the starting XI, with Cahill starting up front and Matthew Leckie pushed out wide. Tommy Oar came in on the left flank and Tom Rogic was deployed in the hole.
Australia started strongly, moving the ball quickly and worrying Ecuador with their pace in attack. Cahill enjoyed an early sight of goal in the sixth minute with a header that glanced just wide of the post.
Two minutes later he improved on that narrow miss. A driving run from Tom Rogic earned Australia a corner, which Tommy Oar swung in from the right. Mark Milligan, stationed on the edge of the area, headed the ball back into danger and Cahill was on hand to nod it home and enter the record books.
In the 16th minute Australia were awarded a penalty when Cahill went down after grappling with Gabriel Achilier inside the area. Jedinak stepped up to slot home the resulting spot kick with ease.
The Socceroos remained relatively untroubled by their opponents as the half progressed, and grabbed a third goal on 32 minutes. A quick break near the half-way line allowed Leckie to advance and swing in a cross, which Cahill dived to connect with and head past Adrian Bone in the Ecuador goal.
Mitch Langerak replaced Mat Ryan in goal for Australia at the break and the South American side made a host of changes, beginning the second half with considerably more purpose.
In the 57th minute their endeavour was rewarded with a goal from Fidel Martinez, who prodded the ball home after being found in a dangerous area by Enner Valencia's pass.
Less than 60 seconds later they had a second and Australia found themselves down to 10 men. Langerak rushed out to try and clear a ball into the area but Valencia got there first, and the Borussia Dortmund man was shown a straight red card after sending the Ecuador forward flying into the air.
The linesman initially raised his flag to signal Valencia was in an offside position but was overruled by referee Lee Probert, who spotted that the last touch came off Jedinak.
Brad Jones became the third player to pull on the gloves for the Socceroos in the game, but he was unable to prevent Segundo Castillo from making it 3-2 from the penalty spot.
The Ecuador onslaught continued as a series of substitutions from Postecoglou, including a debut for Alex Wilkinson, proved unable to stem the tide.
In the 78th minute a counter-attack saw Antonio Valencia advance into the area and cut the ball back for namesake Enner Valencia to guide past Jones.
With the clock ticking down it looked as if Australia would survive to claim a draw, but an error from Wilkinson, who was dispossessed in a dangerous area, allowed substitute Edison Mendez to claim an injury time winner for Ecuador.
The calamitous second-half performance leaves Postecoglou and the Socceroos with some tough questions to answer ahead of their next friendly against South Africa in Sydney on May 26.