Chelsea looks far from conquering their demons in the current Barclays Premier League as they struggled to translate their early dominance into goals at the Britannia Stadium.
The Blues were condemned by a 54th minute strike from Marko Arnautovic.
Defeat was the seventh in their first 12 Premier League matches for the Blues – the first time any defending champions have struggled so badly, as well as a personal unwanted record number of defeats in a league season for Mourinho.
The last time Chelsea lost so many games so early in the campaign, 1978-79, they ended up being relegated – and although they will surely not suffer that same fate this term, they are now 16th in the table, just three points clear of the bottom three.
Arnautovic’s acrobatic goal ultimately proved the difference, as the Austrian forward scored with an excellent finish after 53 minutes.
Pedro shot against the post as Chelsea pushed for a leveller late on, but that was the closest they went to finding an equaliser.
The absent Mourinho made two changes to his starting line-up, bringing in Eden Hazard and Pedro for Cesc Fabregas and Oscar, who both dropped to the bench.
Stoke were unchanged, with Jon Walters starting in attack following the news earlier on Saturday that he had signed a new contract with the club until 2018.
The hosts made a bright start, as Xherdan Shaqiri shot off-target, before Glen Johnson collected a pass from Bojan, turned on to his left foot and sent a placed shot towards the corner to force Asmir Begovic into a diving one-handed save against his former club.
It was then home goalkeeper Jack Butland’s turn to impress when he got up well to push a dipping long-range effort from Ramires over the crossbar.
Walters headed onto the roof of the net after good work from Shaqiri down the right, while Diego Costa’s shot was saved by Butland with his legs prior to half-time, and Stoke then opened the scoring eight minutes after the break.
A superb slide-rule pass from Shaqiri found Johnson in space on the right and the former Liverpool defender’s cross was helped on by Walters before bouncing to Arnautovic. The Austrian netted with an excellent scissor kick – his first home goal in the Premier League for 18 months.
The visiting fans responded immediately with chants in support of their under-pressure manager, and Matic shot straight at Butland as Chelsea sought a response before Hazard lashed a shot off target.
They thought they had levelled soon afterwards when Willian found Pedro and the former Barcelona forward unleashed a left-footed attempt from the edge of the area, but the ball struck the foot of the post and bounced to safety.
Rui Faria and Steve Holland – taking charge of the champions in Mourinho’s absence – brought on Fabregas, Oscar and Loic Remy in the closing stages as they attempted to turn the game around and Hazard shot just wide after a neat passing move with 10 minutes to go.
Walters missed the target with a presentable opportunity to put the game beyond doubt at the other end after being found by substitute Mame Biram Diouf, before Remy – off-balance after being clipped as he attempted to round Butland – passed up the last big opportunity to save Chelsea as their terrible start to the season continued.