Fans poured into the streets of the Czech capital following the Hammers’ victory over Fiorentina, with many already in the city centre after thousands of supporters travelled from the UK without tickets.
But a scuffle broke out after police officers tried to confiscate a lit flare as fans gathered in the Old Town area of the city.
Riot police stormed a group after they lit a second flare, with fans responding by pelting the officers with bottles and missiles.
Earlier in the day Czech police said they had detained at least 16 Italian fans after they attacked West Ham supporters outside a bar, with videos shared on social media showing chairs and fireworks being thrown.
Celebrations were initially good-natured after the match, with revellers hugging and kissing each other and dancing on tables in bars.
Chants of “2-1 to the cockney boys” and “Irons” also broke out as the Londoners welcomed the club’s first trophy in more than 40 years.
The final took place at the Fortuna Arena, which has a capacity of around 19,300, with West Ham receiving an official ticket allocation of 5,000, although many more travelled from the UK to be in the city during the game.
Supporters watched in bars around the city, including a group who went wild at McCarthy’s Pub in the Old Town area from the moment Jarrod Bowen gave the team the lead in the final minute of the second half.
West Ham fan Aaron, 18, said it felt “unreal” to win.
“(I’ve) never felt like it in my life,” he said.
He said his plan for the rest of the night was to “stumble back to the hotel”.
“How we get there I don’t care,” he added.
It came hours after West Ham fans were attacked by Italian supporters in the city centre, prompting police to detain 16 people.
Czech police said three people were injured during the incident, with one police officer being attacked.
One witness said fans of the Italian side were armed with “chains and belt buckles”.
There was also controversy during the match as Cristiano Biraghi of Fiorentina was seen bleeding from the back of the head after he appeared to have been hit by an object thrown from the West Ham stand.
Shortly before the end of the match, the English club put out a statement condemning the behaviour of a “small number of individuals”, adding: “These actions have no place in football, and do not in any way represent the values of our football club and the overwhelming majority of our supporters, who have behaved impeccably in Prague this week and throughout our last two seasons in European competition.”
The club said it would work with police to review the incident and take action against offenders, including implementing lifetime bans.