St Helens (0) 16
Tries: Meli, Graham, Roby Goals: Eastmond, Foster
Harlequins (20) 27
Tries: Dorn, Pryce, Clubb, Koupartisas
Goals: Gale 5 Drop Goal: Gale
Harlequins showed their fine start to the season is no fluke with another big scalp as St Helens again flopped at their temporary new Widnes home.
After being stunned by two tries in the first six minutes, through Luke Dorn and on-loan Wigan centre Karl Pryce, there was worse to come for Saints.
Tony Clubb added another try, Luke Gale adding a third conversion before his penalty earned a 20-0 half-time lead.
Saints got it back to 20-10 but a try from Nick Koupartisas closed the door.
Australian Test prop Josh Perry, hampered by foot and ankle injuries since making his move from Manly, made his delayed St Helens debut.
But Quins, who had lost all their last 10 games with Saints, showed a liking for their hosts' new home at the Halton Stadium - just as they did when they won at Leeds a fortnight ago.
Quins' only previous Super League win against Saints had came at Knowsley Road on the first day of the season in February 2007 when they won 14-6.
But they proved far too strong for a Saints side missing Jon Wilkin, Leon Pryce, both injured on England training camp duty, and Sia Soliola.
It was a magnificent first-half performance that set Quins on their way to a fourth win from their opening five matches, outstanding hooker Andy Ellis combining magnificently with half-backs Luke Gale and Chad Randall.
Quins, who gave debuts to former England winger Mark Calderwood and 20-year-old Wigan trialist half-back Joe Mellor, seized control with those two early tries and never looked like relinquishing their hold.
I thought we were good enough to win by more
The meagre 6,050 crowd were stunned inside three minutes when skipper Rob Purdham brought Dorn onto a delightful inside ball, the full-back easily rounding opposite number Paul Wellens to open the scoring.
Just three minutes later giant centre Pryce, given a first start in the absence of the suspended David Howell, proved unstoppable after taking Randall's pass 10 metres from the Saints line to grab his second try in three appearances.
When Saints managed to put the visitors under pressure their defence was up to the test, Dorn pulling off a last-ditch tackle on Gaskell and Calderwood tackling Francis Meli into touch at the corner.
The Londoners demonstrated far superior finishing when England centre Clubb made the most of some soft defence to touch down midway through the first half.
Winger Meli gave Saints hope when, eight minutes into the second half, he took Lee Gaskell's long pass to cross unopposed at the corner. And a comeback looked on when captain James Graham crashed over as first receiver on the last tackle, Kyle Eastmond converting.
But Roby's forced pass was intercepted by Quins back rower Kouparitsas, who had an unopposed 40m sprint for his first try for the club.
Gale maintained his 100% record by landing his fifth goal, adding a drop goal five minutes from the end before England hooker James Roby grabbed a last-minute consolation try for Saints, Jamie Foster kicking the conversion.
St Helens coach Royce Simmons:
"It was a very ordinary performance. That first half was very disappointing. We were very poor. The second half was a bit better and we scored three tries to one but you can't give 18 points away.
"Our attitude wasn't good enough. They turned up with a lot more energy and a lot more desire. We didn't play too well and I didn't coach too well, obviously.
"It's disappointing when you're in front of your own crowd. They only had about three supporters here I reckon.
"We all have to have a good hard think about what we're doing."
Harlequins coach Rob Powell:
"We don't want to get carried away but I don't think the scoreline reflected the game. I thought we were good enough to win by more.
"There were opportunities to kill the game off, especially at 20-0. We need to learn to do better in those situations because we could get end up getting stung.
"Luke Gale had a dip last week and was disappointed with himself. He got it back tonight, though. He put some great kicks in and showed some control and composure and had a real good crack.
"Karl Pryce is enjoying himself and it showed in the way he played. He's obviously a menace with the ball near their end because he's so big."
St Helens: Wellens; Gardner, Shenton, Lomax, Meli; Gaskell, Eastmond; Graham, Roby, Perry, Clough, Flannery, Puletua.
Replacements: Moore, Dixon, Magennis, Foster.
Harlequins: Dorn; Calderwood, Clubb, Pryce, Melling; Gale, Randall; Ward, Ellis, Wilkes, Burnett, Purdham, Bailey.
Replacements: Temata, Koupartisas, Ambler, Mellor.
Referee: Gareth Hewer (Whitehaven).