Around 50 masked thugs, some of whom were reportedly making fascist salutes, attacked a group of 150 Spurs fans who had gathered in the Smoking Dog pub in Lyon ahead of Thursday's Europa League second leg tie.
Tottenham scored a late equaliser to secure progression against the French side in that match.
Eyewitnesses say the group of attackers smashed doors and threw cast-iron chairs, wooden objects, and a lit flare into the pub, which is popular among ex-pats in the French city.
The French club have responded with a statement, saying: "Olympique Lyonnais deplore the incidents overnight in the Saint-Jean district between the supporters of Tottenham and the 'pseudo' supporters of Lyon who absolutely do not represent the club.
"Olympique Lyonnais apologises to Tottenham and its supporters, for the inadmissible acts which degrade the image of the town of Lyon.
"Olympique Lyonnais call on the French justice system to impose severe sanctions for these reprehensible acts."
Tottenham confirmed that three of their fans sustained 'minor injuries' in the attack, and that a number of arrests had been made.
It is the second time that Tottenham fans have been targeted in the last three months after they were ambushed inside a pub in Rome on the eve of their game against Lazio.
A Tottenham spokesman said earlier: "Club officials attended an incident last night in Lyon. A group of around 50 people confronted fans.
"Spurs officials and stewards will be in the city throughout the day, along with matchday French police ahead of kick-off."
Dave Eales, landlord of the pub, said: "At 10.18 the pub was rammed with Tottenham fans watching the Champions League on the television. The front of the pub, which is made up of reinforced glass, was attacked by 20-25 people.
"They threw projectiles through the windows. There was a stand-off. They didn't get in to the bar. Then it calmed down. Then they came back a second time and it all started again.
"There were three injured Tottenham fans taken away by ambulance. One of them had a head injury. I'm not sure how bad it was."
Spurs fan and journalist Aidan Radnege, who was in the bar at the time of the attack, said: "They came in making Nazi salutes. It was frightening. Rome was fresh in everyone's minds. Everyone realised this was serious."