Jarrod Bowen's late goal sealed a 2-1 win against Fiorentina to see the Hammers win their first trophy since the FA Cup in 1980.
The victory sparked jubilant scenes in the West Ham crowd at the Eden Arena in the Czech capital.
Fans then took to the streets of Prague to celebrate, with many visiting supporters travelling to the city without a match ticket.
A video on Twitter captured one fan waving a flare in the air as they celebrated their team's win.
However, police are said to have already confiscated one flare earlier and, in the video, riot police could be seen storming towards the supporter.
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West Ham fans threw bottles and missiles at them in response in scenes that were similar to what happened before kick-off.
Earlier in the day, both sets of fans clashed with each other in Prague just hours before the final took place.
Fiorentina ultras are said to have attacked West Ham supporters with fireworks and weapons.
Czech police tweeted to show at least 16 Fiorentina fans arrested amid the incidents in Prague.
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Speaking to talkSPORT the following morning, former West Ham man Anton Ferdinand said: "Yeah obviously it's not great to see the fans clashing with the fans and the police.
"You know, we don't win trophies regular. For me personally, I don't condone it, I don't want to see it. But we can't allow it to overshadow what it is that we done last night which was create history."
He added: "I'd like to think that [a minority of fans clashing].
"The West Ham fans that ain't involved in this stuff will be the ones trying to calm it down but as I said, I wish everyone safe, I hope everyone gets back to London safe for tonight's parade."