Fulham put a huge dent in Tottenham's Champions League ambitions when former Spurs striker Dimitar Berbatov scored the only goal after 52 minutes.
FA Cup semi-finalists Wigan Athletic stayed in the relegation zone despite Arouna Kone scoring a last-minute goal in a 2-1 home win over Newcastle United and Sunderland continued to flirt with danger after drawing 1-1 with 10-man Norwich City.
The Canaries battled for more than an hour for their point after they were reduced to 10 men when goalkeeper Mark Bunn was sent off for handling outside the penalty area.
Most of the attention was focused on the two London derbies with Spurs and Chelsea involved in an increasingly tight battle for a top-four finish and a place in next season's Champions League.
West London prevailed in both games with Chelsea's win moving them on to 55 points, one more than Spurs, who have played one more match.
Fulham's victory, only their third at White Hart Lane in the League since they first played Spurs there 104 years ago, was enough to consolidate their mid-table place and leave Spurs fans nervously dreading another end of season collapse.
Chelsea, on the other hand, have regained form despite the unrest among fans surrounding interim coach Rafa Benitez and their deserved victory followed the 2-2 comeback draw with Manchester United in the FA Cup and a 3-1 win over Steaua Bucharest in the Europa League.
"It is a long race," Benitez told Sky Sports.
"We have to carry on, win our next game and see what the others do. We have to be pleased because we scored two goals and kept a clean sheet, but we could have finished it earlier."
Lampard struck his milestone goal after 19 minutes against his former club after converting a cross from Eden Hazard and the Belgian added the second in the second half to seal the points.
While Chelsea are battling through their crisis, Spurs seem to be entering one.
After going 12 league matches unbeaten and playing some excellent football to climb to third, Spurs have now lost three times in eight days following their 3-2 league defeat at Liverpool and a 4-1 Europa League loss to Inter Milan.
Spurs did squeeze into the quarter-finals of the European competition on away goals, but there was no reprieve against Fulham who defended superbly after taking the lead and Mark Schwarzer made two brilliant late saves to deny substitute Jermain Defoe.
Fulham manager Martin Jol, the former Spurs coach, said he took no personal satisfaction from the win, but was delighted with the three points.
"They are a very strong team and you come here hoping for a point, but we got all three today and I am very happy. I still think Spurs will finish in the top four, but we deserved it today."
Spurs manager Andre Villas-Boas told reporters he did not think the team's well documented collapse last season would have an impact on the run-in.
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