Hooker Schalk Brits and flanker Will Fraser scored the tries with England fly-half Owen Farrell kicking their other 17 points.
Fly-half Nick Evans kept Harlequins in contention into the second half with four penalties from five attempts but the reigning Premiership champions were second-best as they strove in vain to repel the Sarries' attack - or breach their rock-solid defence.
Saracens went into the match one point ahead of Leicester, who had moved into second with their win over Exeter 24 hours earlier, and four clear of third-placed Quins.
Both sides wheeled out their big guns with players back from RBS 6 Nations duty.
England's Farrell, Alex Goode, Chris Ashton, Brad Barritt and Mako Vunipola returned for Sarries, along with Scotland captain Kelly Brown.
Harlequins had Mike Brown, Danny Care, Joe Marler and captain Chris Robshaw back in their starting line-up.
Saracens took the early initiative with Vunipola almost powering his way through before three players hauled him down just short of the line.
The early pressure produced a third-minute penalty for Farrell, cancelled out three minutes later by Evans.
The New Zealander kicked Quins into a 6-3 lead after former England prop Matt Stevens was caught offside but Farrell levelled the scores after ex-England number eight Nick Easter went through on scrum-half Richard Wigglesworth at a ruck.
An excellent break by Ashton split the visiting defence and released flanker Fraser, who was denied a try by Brown's cover tackle.
The combined efforts of the Quins defence prevented Fraser from recycling the ball at the cost of a yellow card for Marler.
Sarries capitalised by scoring 11 points while the prop was in the sin bin. Farrell landed the resulting penalty before kicking his fourth in the 23rd minute.
A slick five-man handling move opened up the depleted Quins defence before Brits forced his way over for the game's first try but Farrell missed the conversion.
Marler returned as the visitors were awarded a 30th-minute penalty, kicked by Evans after Sarries number eight Ernst Joubert offended at the breakdown.
But the New Zealander then missed a penalty opportunity to reduce the deficit before Farrell was off-target on the stroke of half-time.
Saracens withdrew their former Harlequins winger David Strettle, who had suffered a leg injury late in the first half, at the interval, replacing him with United States international Chris Wyles.
Five minutes into the second half Evans made amends for his earlier miss to cut the gap to five points after the back-pedalling Saracens scrum was penalised.
Saracens responded with Brown, Goode and Ashton combining to put Harlequins in trouble again. Playing the advantage after Quins failed to release Ashton, Farrell produced a superb cross-kick into the arms of the unchallenged Fraser who touched down. Farrell converted to give Saracens a 24-12 lead.
Farrell missed a 58th-minute penalty shot but made no mistake 10 minutes later to stretch his side's lead to 15 points.
In the closing stages, Ashton looked fortunate to escape with only a yellow card for a high tackle on Harlequins' replacement flanker Maurie Fa'asavalu after referee Greg Garner asked the television match official to review the incident.
Harlequins tried desperately to make their one-man advantage pay but Saracens kept them out.