Arsenal's hopes of a third successive victory were dashed in a 3-2 defeat at Stoke City where they trailed 3-0 at halftime and Liverpool were held to a 0-0 home draw by Sunderland -- one of three goalless stalemates.
Undefeated in 23 matches in all competitions since April's Champions League semi-final against Atletico Madrid, Chelsea proved far from invincible as 10-man Newcastle survived a late barrage to prevent the visitors setting a record unbeaten run.
Few could deny Newcastle a deserved win that lifted them to seventh in the table, although Chelsea manager Jose Mourinho said his side had been unlucky.
The hosts lost goalkeeper Rob Elliot to injury at halftime, replaced by young rookie debutant Jak Alnwick, and had to man the barricades with only 10 men when Steven Taylor was dismissed after getting a second yellow card 10 minutes from the end.
Substitute Cisse, who replaced Remy Cabella after the break, put Newcastle in front after 57 minutes following a slip by Gary Cahill and struck again on the break 20 minutes later, seconds after Eden Hazard was denied an equaliser by the woodwork.
Didier Drogba's majestic header halved the deficit late on but Newcastle survived six minutes of stoppage time and Chelsea's 14-match unbeaten start to the season, which had drawn comparisons with the Arsenal Invincibles of 2003-04, was over.
"We were very unlucky, even more than last season," Mourinho, beaten 2-0 at Newcastle in the last campaign, told the BBC. "Only one team wants to win, only one team plays to win, but that team doesn't score and they go and cross the midfield line and score a goal and after that we have to chase the game which we did, which gave me lots of pride."
THREE POINTS
Champions Manchester City can close the gap at the top to three points if they beat Everton later on Saturday.
Third-placed Southampton host Manchester United, in fourth, on Monday.
Arsenal fell behind to a Peter Crouch goal after 19 seconds at Stoke and Bojan and Jon Walters made it 3-0 by halftime.
Santi Cazorla's penalty and a goal from Aaron Ramsey gave Arsenal hope after the break but the damage was already done for the visitors who had Calum Chambers sent off.
"Once we were 3-0 down, we had a mountain to climb. We did climb, but a bit unlucky I must say," manager Arsene Wenger said.
Skipper Steven Gerrard was left on the bench by Brendan Rodgers as Liverpool laboured at Anfield.
Queens Park Rangers beat Burnley 2-0 to climb out of the relegation zone.
Tottenham Hotspur drew 0-0 with Crystal Palace, as did strugglers Hull City and West Bromwich Albion.
Chelsea, with Diego Costa back in attack after missing the midweek win over Tottenham Hotspur through suspension, dominated for long periods but were unusually profligate in front of goal.
Willian should have scored but shot narrowly wide and the Brazilian forced Elliot into a diving save. Costa also failed to capitalise from a couple of dangerous situations.
Elliot limped off at halftime, allowing 21-year-old Alnwick to make his first competitive appearance.
However, it was Newcastle's second substitution that proved the most telling as Cisse strode on.
The Senegal striker tapped in Sammy Ameobi's low cross after Cahill failed to clear. Chelsea responded with Hazard hitting the post but Newcastle went further ahead after a counter-attack ended with Moussa Sissoko setting up Cisse for another tap-in.
Taylor's sending-off and Drogba's second goal of the week silenced the home crowd but Mourinho was left still waiting for his first away league victory over Newcastle.
(Editing by Ed Osmond and Toby Davis)
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