Conor O'Shea's men briefly threatened a second-half comeback with a try from full-back Mike Brown, who impressed in difficult circumstances.
But ultimately Toulouse had too much power and panache.
The French giants created a try in each half for the Fijian wing Timoci Matanavou while Luke McAlister kept Harlequins subdued with three penalties and a conversion.
England's interim head coach Stuart Lancaster was among the sold-out crowd at The Stoop to cast an eye over Harlequins' crop of exciting youngsters.
Loose-head prop Joe Marler endured a torrid time opposite the giant Samoan Census Johnston until he was carried off on a stretcher.
Chris Robshaw, seen by many as an England captaincy candidate, had his work cut out opposite a Toulouse back row that included imperious French skipper Thierry Dusautoir and man of the match Louis Picamoles.
There were second-half flashes from try-scorer Brown, from wing Ugo Monye and scrum-half Danny Care to excite Lancaster as Quins briefly threatened a comeback.
Toulouse are often unpredictable on their travels but they laid down a European marker tonight, edging clear of Harlequins to deny them a losing bonus point.
Toulouse's power up front was evident early on but Harlequins' retreating pack escaped once, when referee George Clancy penalised Toulouse scrum-half Luke Burgess for a crooked feed.
Nick Evans cancelled out McAlister's early penalty and Harlequins should have taken the lead after a surging blind-side break from Sam Smith.
Centre Benjamin Urdapilleta carried Harlequins into the 22 and Care opted for a quick tap penalty when Toulouse were penalised for not rolling away.
But just five metres from the Toulouse line, Harlequins were guilty of holding on and a golden chance for an early lead was blown. They never came as close again.
Toulouse cruised into an 11-3 lead, with McAlister given an armchair to direct traffic at fly-half courtesy of their crushing power up front.
Matavanou's first try began with a rumble from Johnson. McAlister's long pass picked out Picamoles and Dusautoir offloaded delightfully for the Fijian to score in the corner.
Toulouse were purring in possession and McAlister landed his second penalty.
Harlequins were rocking but they clung on to the break with some gutsy scramble defence.
McAlister launched a scything 50-metre break after Toulouse had won a scrum against the head. Yannick Jauzion and Yannick Nyanga were in support but Harlequins regrouped.
Harlequins sent on Monye for the second half and his injection of energy lifted the team.
Centre Matt Hopper made a delightful break, carving through the Toulouse line and then offloading deftly out the back of his hand before Brown chipped on.
A Toulouse knock-on gave Harlequins a platform within striking distance.
Care opted for another quick tap penalty but this time it worked as Marler sent Brown over for the try.
Evans' conversion brought Harlequins back to within a point but any hope of a home comeback was soon snuffed out with another McAlister penalty.
Toulouse duly wrapped up a deserved victory when McAlister's popped pass sent Vincent Clerc streaking away and Matanavou scored in the corner, despite a noble effort from Brown to tackle him into touch.
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