Manchester City trimmed Premier League leaders Chelsea's advantage to three points by beating Everton 1-0 on Saturday, but at the cost of a knee injury to talisman Sergio Aguero.
Chelsea lost their unbeaten record after losing 2-1 at Newcastle United earlier in the day and defending champions City took advantage by beating Everton thanks to Yaya Toure's first-half penalty.
But the sight of Aguero limping off in tears after injuring his left knee in the early exchanges raised stark fears for Manuel Pellegrini's side, who face a crucial trip to Roma in the Champions League on Wednesday.
"We dominated the game and I think that we deserved to win," City manager Pellegrini told Sky Sports.
"Sergio has a problem with his knee ligament. We'll see tomorrow (Sunday) how serious it is, but it's not good news. I don't think that he will be able to play next week."
The game at the Etihad Stadium was only a matter of minutes old when top scorer Aguero tumbled under a challenge from Muhamed Besic, and he hobbled down the tunnel shortly after.
City made the breakthrough in the 24th minute, with Toure finding the bottom-left corner from the spot after Phil Jagielka was adjudged to have impeded James Milner.
The visitors improved after Ross Barkley came on, but City goalkeeper Joe Hart produced a stunning one-handed save to thwart Romelu Lukaku and safeguard a fifth successive win in all competitions.
Earlier, substitute Papiss Cisse claimed a brace as Chelsea's hopes of completing the season unbeaten were dashed by defeat at Newcastle.
Cisse scored twice in the second half and despite Steven Taylor being sent off for Newcastle and Didier Drogba replying late on for the visitors, Alan Pardew's side held on for a third consecutive home win over Chelsea.
"My team lost the way I like to lose, which is to give everything and being unlucky. Only one team played to win," Chelsea manager Jose Mourinho told the BBC.
"I'm not obsessed with records and statistics. That's not for me. I want to win the league."
With top scorer Diego Costa back in the team after suspension, Chelsea enjoyed the best of the first half at St James' Park, only to fall behind in the 57th minute.
Moussa Sissoko fed Sammy Ameobi on the Newcastle left and with Gary Cahill failing to cut out the 22-year-old's low cross, Senegal striker Cisse pounced to tap home from inside the six-yard box.
Stoke sink Arsenal
Shortly after Eden Hazard had hit the post for Chelsea, Cisse made it 2-0 with 12 minutes remaining by rolling the ball home from Sissoko's square pass.
Home captain Taylor saw red after being shown a second yellow card for upending Andre Schuerrle before Drogba halved the deficit with a header from a Cesc Fabregas free-kick.
But Newcastle survived six nervous minutes of stoppage time to deny Chelsea a club-record 24th game without defeat.
"That was about character and discipline against probably the best team in Europe at the moment," said Pardew.
"We're delighted to have given a little gee-up to the Premier League. I'm sure Jose won't agree."
As well as City, Chelsea's loss will also offer encouragement to third-place Southampton and fourth-place Manchester United, who meet at St Mary's on Monday.
But Arsenal squandered an opportunity to take advantage by losing 3-2 at Stoke, leaving Arsene Wenger's side 13 points off the pace in sixth.
Peter Crouch put Stoke ahead after 19 seconds at the Britannia Stadium, where Arsenal have tended to struggle in recent seasons, and further goals from Bojan Krkic and Jonathan Walters gave the hosts a 3-0 half-time lead.
A Santi Cazorla penalty and an Aaron Ramsey volley took Arsenal to the verge of a comeback, but the visitors' momentum disappeared after defender Calum Chambers was shown a second yellow card for pulling back Bojan.
"Defensively, we missed the start of the game," said Wenger. "Once we were 3-0 down, we had a mountain to climb. We did climb, but were a bit unlucky, I must say."
Liverpool saw a three-game winning run come to an end with a disappointing 0-0 draw at home to Sunderland, while Tottenham Hotspur were held to a goalless draw by Crystal Palace at White Hart Lane.
Queens Park Rangers climbed out of the relegation zone by winning 2-0 at home to Burnley, with Charlie Austin scoring one goal and making another against his former club before being sent off for two bookings.
Hull City, who drew 0-0 at home to fellow strugglers West Bromwich Albion, dropped into the bottom three.