It was Chelsea fifth defeat in the EPL this season, but the repercussions for Mourinho could be even more serious.
With his side trailing 1-0 at halftime, Matic dismissed and with a Cesc Fabregas equalizing effort ruled out, Mourinho reportedly confronted referee Jonathan Moss in the tunnel at Upton Park.
He spent the second half in the directors' box after being ejected, a fate which also befell first team coach Silvino Louro.
Mourinho refused to speak to the media after the match, but earlier this month he was fined £50,000 ($75,000) and given a suspended stadium ban for his criticism of another referee in a loss to Southampton.
It was a tale of familiar failings for Chelsea, who have leaked goals in the campaign, with slack defense from a corner allowing Mauro Zarate to power home the opener for West Ham.
Chelsea might have leveled through Fabregas -- a marginal offside decision -- and Kurt Zouma's header was just millimeters from crossing the line, goal line technology confirmed.
But Matic went after bringing down Diafra Sakho just before the break to earn a second yellow to make its task even more difficult.
To its credit, 10-man Chelsea fought back to level through Gary Cahill, but the Hammers sealed three points when Andy Carroll powered home a header - his first goal in the EPL in 279 days after injury setbacks putting his side up to third.
Later Saturday, Arsenal took over at the top of the standings with a 2-1 home win over Everton.
Arsene Wenger's team leads Manchester City by a single point, but fully 11 points ahead of Chelsea after just 10 games.
City plays fourth-placed Manchester United in a crunch derby match Sunday hoping to regain the leadership.
Arsenal scored two goals in the space of two first half minutes, both headers, from Olivier Giroud and Laurent Koscielny, to take command at the Emirates.
But England international Ross Barkley pulled one back before the break and the result was in doubt to the last, Everton losing Gareth Barry to a second yellow card near the final whistle.
In other games, Jamie Vardy scored in his seventh straight EPL game to give unheralded Leicester a 1-0 win over Crystal Palace to stay fifth, while the pressure is mounting on manager Tim Sherwood after Aston Villa's 2-1 home defeat to Swansea.
Real goes top
Cristiano Ronaldo scored the opener in Real Madrid's 3-1 win at Celta Vigo, leapfrogging the home side at the top of the La Liga standings.
Real led 2-0 after 23 minutes through Ronaldo, his 12th in as many games this season, and Danilo, but relied on goalkeeper Keylor Navas to repel an impressive home side, who had a string of shots on target in the first half
Even after Celta was reduced to 10 men just 12 minutes into the second-half when Gustavo Cabral was dismissed for a second yellow card, it still pushed forward and Nolito grabbed a deserved goal five minutes from time.
The result was in the balance until Marcelo scored for Real with the final kick of the match to seal the three points.
Barcelona can draw level with Real on points with a home win over Eibar Sunday.
Meanwhile, Bayern Munich made it 10 win wins from 10 in the Bundesliga as Arjen Robben made a successful return from injury.
Robben scored the opener in the 4-0 win over FC Cologne which leaves the German champions 10 points clear of Borussia Dortmund, who play Sunday.
It was the 1,000th Bundesliga win for the German powerhouses, who suffered a rare setback when beaten 2-0 by Arsenal in the Champions League in midweek.
Normal service was quickly resumed as Dutch star Robben netted after 35 minutes with Arturo Vidal doubling the lead five minutes later.
After the break, Robert Lewandowski kept up his incredible scoring spree, 13 in nine league games this term, and was later fouled for the penalty which was converted by Thomas Mueller to complete the rout.