The four-time winners led just 12-7 at the interval thanks to quick-fire tries from Florian Fritz and Yannick Nyanga.
The Ospreys hit back with a try from Kahn Fotuali'i but the second half was a one-team affair as Vincent Clerc, Census Johnson, Yoann Huget all crossed over.
The visitors again responded with a try, this time from Ryan Bevington, but it was too little too late.
The victory sees the French giants stretch their lead at the top of the group to eight points with Leicester set to face Benetton Treviso tomorrow.
Luke McAlister fired an early penalty wide but Toulouse quickly established a lead thanks to Fritz.
The French hosts looked to launch an attack from the top of a lineout which broke down, but Fritz pounced on the loose ball and sliced through the Ospreys' defence.
McAlister slotted the conversion and seven minutes later they doubled their advantage.
Again, Toulouse were fortunate to capitalise on disarray at the lineout. Gary Botha overthrew and James King flapped the ball towards the Ospreys but it fell straight to Nyanga, who raced home.
But the Welsh region fought back, with ever-present Kahn Fotuali'i and Ashley Beck leading the charge.
And it was the in-form duo that manufactured the Ospreys' opening score. Beck put his side on the front foot with a strong charge that earned a penalty, Fotuali'i caught Toulouse off guard with a quick tap to race clear.
The Welsh region continued to pile on the pressure but Toulouse weathered the storm to go into the break leading 12-7.
But the French side came out firing following the break and their giant pack steamrolled the Ospreys.
They could have hit back within minutes of the restart as Toulouse flooded forward while chasing a McAlister chip but Fotuali'i intervened.
Toulouse continued to dominate and could have been awarded a penalty try following a succession of scrums, but the Ospreys survived and Justin Tipuric snatched a vital turnover.
But Toulouse were relentless and they came close once again after Medard collected McAlister's cross kick.
They were eventually rewarded for their hard work as Picamoles broke from the back of scrum.
The giant number eight charged towards the Ospreys before releasing Burgess with an offload. Clerc received the ball out wide with plenty of work to do, but he rounded Eli Walker to squeeze in the corner.
McAlister failed to add the conversion but Toulouse did not let up with Picamoles continuing to run riot.
After receiving the ball from Albacete he drew in three defenders before sending Johnson over in the same corner.
Doussain faired no better than McAlister from the touchline but the try had sealed the bonus point and established a commanding 22-7 lead.
And there was still time for a fifth try with Doussain and Medard combining for Huget to dance through the Ospreys defence.
To their credit the Welsh region refused to throw in the towel and they hit back with a score of their own as Bevington and Tipuric combined with a football style one-two for the prop to crash over.
Matthew Morgan converted but the try was merely a consolation and Toulouse rubbed salt into their wounds with a Doussain penalty at the death.
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