During his two spells in charge of the Blues, Mourinho turned the Bridge into a fortress as the club lifted three Premier League titles.
But when he has gone back to his old stomping ground as a visiting boss, things have not panned out so well.
Indeed, in five trips across the Premier League and FA Cup, Mourinho is yet to taste victory when in charge of a domestic rival.
After this weekend's reverse left Spurs four points adrift of his old club, we look at Mourinho's tale of woe in familiar surroundings in west London.
PREMIER LEAGUE: CHELSEA 4-0 MANCHESTER UNITED (OCTOBER 23, 2016)
The Portuguese's first return to Chelsea in the top flight was a punishing one indeed.
Taunted by the home faithful, Mourinho saw his United side picked apart, with the writing on the wall from the moment Pedro opened the scoring inside the opening minute.
Gary Cahill doubled the hosts' lead before half-time, with Eden Hazard and N'Golo Kante rubbing salt in the wound in the second half.
It was Mourinho's heaviest loss in any competition since he oversaw a 5-0 defeat for Real Madrid against Barcelona six years earlier.
— Chelsea FC (@ChelseaFC) October 23, 2016
FA CUP: CHELSEA 1-0 MANCHESTER UNITED (MARCH 13, 2017)
Mourinho was in a fiery mood and clashed with opposite number Antonio Conte on the sidelines, with the action on the pitch doing little to improve his frame of mind.
Ander Herrera saw red before the interval and the two managers went toe-to-toe soon after, with Mourinho claiming Marcos Alonso had taken a dive.
It was left to Kante to settle matters six minutes into the second half, the midfielder beating David de Gea to see his side progress in the competition.
Remarkably, United had just 28 per cent of possession in the quarter-final tie.
PREMIER LEAGUE: CHELSEA 1-0 MANCHESTER UNITED (NOVEMBER 5, 2017)
There was no handshake between Mourinho and Conte at the end of this match, with the Italian prevailing once again.
The out-of-sorts Alvaro Morata scored the winner 10 minutes after half-time, with Kante again influential for the home side.
Asked about the failure to greet his opposite number in the customary manner at the end of the contest, Mourinho appeared defiant.
"You have to have the respect on the pitch not outside the pitch," he told Sky Sports.
FULL-TIME Chelsea 1-0 Man Utd
— Premier League (@premierleague) November 5, 2017
PREMIER LEAGUE: CHELSEA 2-2 MANCHESTER UNITED (OCTOBER 28, 2018)
This was the most heated of the lot, Mourinho at first deflated by Ross Barkley's 96th-minute leveller and then enraged by the celebrations on the Chelsea bench.
Technical assistant Marco Ianni was the one who riled Mourinho, who jumped out of his seat and had to be held back by a combination of stewards and members of United’s backroom staff.
Anthony Martial's double had put United on course for victory after Antonio Rudiger's early opener.
But Maurizio Sarri's team had the final say in dramatic fashion.
PREMIER LEAGUE: CHELSEA 2-1 TOTTENHAM (FEBRUARY 22, 2020)
Needing a win to leapfrog Chelsea in the table and advance their hopes of Champions League qualification, Spurs never really got going.
Olivier Giroud broke the deadlock 15 minutes in, while Alonso made it 2-0 shortly after the restart.
A shaven-headed Mourinho may otherwise have been pulling his hair out at such a lacklustre display, with Antonio Rudiger's unfortunate late own goal failing to paper over the cracks for Spurs.
The 57-year-old is not likely to look forward to his next trip back to the Bridge. In contrast, Frank Lampard was able to celebrate becoming the first boss to beat a side managed by Mourinho home and away in a single league season.
Photo Getty Images Caption: Jose Mourinho (centre)