It was the latest in a long line of European encounters between the two sides, going all the way back to the first European Cup final between Toulouse and Cardiff RFC.
On every subsequent occasion the home side prevailed but Danny Wilson’s side tore up the history book as they ground out a hard-fought but deserved win in the south of France.
The Blues trailed 15-10 at the break with Romain Ntamack and Antoine Dupont cancelling out Nick Williams’ earlier effort.
However, Wales' Capital Region caused the French giants a plethora of problems with ball in hand and Macauley Cook finished a vital try with Jarrod Evans slotting the conversion to take the lead.
Both sides enjoyed periods of pressure in a ferocious half, but Evans' extras proved crucial, as the Blues ensured a perfect start to their European campaign.
Toulouse enjoyed all the early pressure after Cardiff Blues failed to secure the kick-off at a lively Stade Ernest Wallon.
The home side’s early dominance almost paid off after five minutes as they broke down the right but what could have been a try-scoring off-load drifted forward.
They continued to impose themselves in a ferociously physical opening period before the Blues enjoyed their first attacking opportunity with Matthew Morgan easing onto the outside from inside his own 22 and finding Rey Lee-Lo in support.
Toulouse opened the scoring on 11 minutes when replacement Romain Ntamack slotted a simple penalty following an early tackle from Nick Williams.
Wilson’s side responded well and booted a scrum penalty to the corner minutes later. Macauley Cook won the ball and they launched a driving lineout which ground forward before surging left illegally.
Once again they went to the corner and once again the maul rumbled left but this time the Blues managed to maintain forward momentum and Williams crashed over the whitewash.
Evans converted the try to give his side a 7-3 lead after 16 minutes.
With their tails up, Cardiff Blues continued to threaten with Blaine Scully and Alex Cuthbert carrying with venom and Lee-Lo with his usual elusive footwork.
Their attacking enterprise was rewarded on 21 minutes and Evans slotted a neat penalty to stretch the Blues’ lead.
Toulouse were next to flex their forward muscle, kicking a pair of penalties to the corner and powering forward. Cardiff Blues defended well and just about held the four-time Heineken Cup winners at bay as they went through the hands to the left.
The Blues brought a third driving lineout to a halt and then forced a knock on as Toulouse’s giant pack hammered away at close-range.
Tomos Williams cleared but he could not find touch and Maxime Médard scythed through on the counter-attack. He was eventually dragged down but the damage was done as the ball moved right to Gael Fickou, who put Ntamack away for a converted try.
Wales’ Capital Region were dealt a further blow when Cuthbert was perhaps harshly sin-binned for a high-tackle.
Star-studded Toulouse continued to throw everything at Cardiff Blues, who fought fire with fire, as both sides struggled to cope with the pace and physical nature of the game.
A fine break from Morgan, who then sent a fine clearance into the Toulouse half, temporarily relieved the pressure but the Blues were dealt a major blow as half-time approached.
Willis Halaholo, moments after coming on for Garyn Smith, attempted to thread a kick through from the half-way line but the ball rebounded off a defender’s foot and bounced fortuitously to Antoine Dupont, who cantered down the right wing.
Dupont was unable to convert but his try had given the French hosts a 15-10 lead.
The Blues had the opportunity to hit-back with a penalty shortly after but they opted for the corner and while they won the lineout and launched a drive, they were pinged for obstruction and Toulouse survived.
Trailing by five-points, the Blues made a lively start to the second-half with Tomos Williams threatening around the fringes and the forwards carrying hard but they were unable to turn pressure into points as Toulouse flooded the breakdown.
However, Cardiff Blues continued to press and they finally got their reward with a stunning try on 52 minutes.
Evans took the ball to the line and managed to slip an offload to the onrushing Dillon Lewis, who drew Medard and popped a try-scoring pass to Cook.
The 21-year-old fly-half added the extras to give his side a deserved lead, much to the delight of the travelling support.
Toulouse rallied following the score and stormed into the Blues half with a succession of off-loads and powerful carries before the ball was knocked forward.
There was a tense moment as referee Tom Foley went to the TMO following a thunderous hit from Lee-Lo in midfield but replays showed the Samoan international made contact with the chest and wrapped an arm.
The Blues continued to cause Toulouse all manner of problems on the outside with Morgan and Smith causing chaos on the counter-attack.
Another Morgan break, followed by an intelligent kick through as he ran out of support almost paid dividends as Medard fluffed his lines and Scully pounced on the ball.
Cardiff Blues recycled the ball and went through two phases before play broke down as the encounter continued to lose shape.
With the hour mark passing, Toulouse raised the tempo and threatened with a spree of frenetic attacks but still the Blues clung on with Morgan making a pair of try-saving tackles.
They broke out of their half with the ever-impressive Lee-Lo dummying and stepping past several defenders.
That was to be his last action as Steve Shingler entered the fray but within moments the replacement centre was sent to the bin after a confrontation with Toulouse back-row Rynhardt Elstadt.
It was undoubtedly a blow but they benefitted as Foley reversed the previous penalty, allowing Evans to drive the French outfit into their own 22.
Now it was the visitors that pressed as they looked to stretch their lead but mistakes crept in at vital moments.
There were further signs of encouragement however as a youthful front-row of Brad Thyer, Ethan Lewis and Dillon Lewis had the nudged at the set-piece.
Lively scrum-half Dupont looked for a way down the blindside but was taken down, before Josh Navidi made a crucial interception from the offload with four minutes left on the clock.
As the game entered its final minutes, Cardiff Blues looked to play down the clock and maintain possession, but a knock-on gave Toulouse one final scrum.
The home side looked to attack from deep, but good defensive combination from Shingler and Smith held up the attacker and turned over possession to bring a classic encounter to an end.