Problems in Seville are believed to have started before the game with both sets of supporters throwing objects at each other while police moved in to separate the supporters while the game progressed on the field.
Seville had asked Uefa last week if the game could be moved due to its proximity to Easter festivities in the city but the governing body rejected their request.
It is reported that seven Spurs fans and one police officer required hospital treatment for injuries suffered during the incident.
Tottenham said in a club statement: "Our initial reports suggest that there was no fan-to-fan fighting at any stage of the proceedings. As such we are seeking explanations as to why the police reacted in the way they did with our fans.
"We will be cooperating fully with Uefa, the British Embassy and the Spanish authorities to understand why this has happened."
Last night's scenes echo the events at Rome's Stadio Olimpico where fans of both sides were seen charging towards each other on either side of a segregating fence, which prompted Italian riot police to intervene.
As many as 18 visiting fans and two Roma supporters were taken to hospital and, as expected, Uefa will launch an investigation to work out exactly how the situation flared up so dramatically.
"We will be waiting for the delegate's report and the control and disciplinary body will be looking at the television images to see the dynamics of what actually happened," Uefa spokesman William Gaillard said.
"In Italy, the police are in charge of security in the stadium because the grounds are municipal. Stewards who may be better able to cope with the situation have nothing to do with it."
There was also a stark warning for the Premiership side, who could face sanctions if their policing of the game and ticket allocations are found to have had a hand in sparking the trouble.
"We will have to see what role Manchester United fans had in the incidents because they had some problems in Lens earlier this year," Gaillard added.
In a statement released by the club, Manchester United said: "There were clearly some very disturbing scenes in the stadium on Wednesday night.
"Until we have had chance to discuss the situation with the British Embassy in Rome and the Italian authorities and to understand the cause, it would be inappropriate to comment."
A statement from Uefa read: "Uefa has opened an investigation into the incidents that occurred at the UCL [Champions League] match AS Roma-Manchester United FC.
"Uefa is currently gathering evidence and will be studying the official reports of the referee, delegate and security officer in detail before announcing any further action," the statement concluded.
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