Police broke down doors to force entry into voting stations as defiant Catalans shouted "Out with the occupying forces!" and sang the anthem of the wealthy northeastern region. In one incident in Barcelona, police fired rubber projectiles.
Catalan officials said 337 people had been injured in the police crackdown. Officers in riot gear hit people with batons and forcibly removed would-be voters, including women and the elderly, from polling stations.
The referendum, declared illegal by Spain's central government, has thrown the country into its worst constitutional crisis in decades and deepened a centuries-old rift between Madrid and Barcelona.
Despite the police action, hundreds-strong queues of people formed in cities and villages throughout the region to cast their votes. At one Barcelona polling station, elderly people and those with children entered first.
"I'm so pleased because despite all the hurdles they've put up, I've managed to vote," said Teresa, a 72-year-old pensioner in Barcelona who had stood in line for six hours.
The ballot will have no legal status as it has been blocked by Spain's Constitutional Court and Madrid for being at odds with the 1978 constitution.
A minority of around 40 percent of Catalans support independence, polls show, although a majority want to hold a referendum on the issue. The region of 7.5 million people has an economy larger than that of Portugal.
However much voting takes place, a "yes" result is likely, given that most of those who support independence are expected to cast ballots while most of those against it are not.
Organisers had asked voters to turn out before dawn, hoping for large crowds to be the world's first image of voting day.
"This is a great opportunity. I've waited 80 years for this," said 92-year-old Ramon Jordana, a former taxi driver waiting to vote in Sant Pere de Torello, a town in the foothills of the Pyrenees and a pro-independence bastion.
The Catalan government said voters could print out ballot papers at home and lodge them at any polling station not closed down by police.
Elsewhere, people were not able to access the ballot boxes. In a town in Girona province where Catalan leader Carles Puigdemont was due to vote, Civil Guard police smashed glass panels to open the door and search for ballot boxes.
"The unjustified, disproportionate and irresponsible violence of the Spanish state today has not only failed to stop Catalans' desire to vote ... but has helped to clarify all the doubts we had to resolve today," he said.
The Madrid government said 11 police officers were injured in the clashes.
Nicola Sturgeon, the pro-independence leader of Scotland, which voted to remain part of the United Kingdom in a 2014 referendum, said she was concerned by the images she was seeing from Catalonia.
"Regardless of views on independence, we should all condemn the scenes being witnessed and call on Spain to change course before someone is seriously hurt," she said on Twitter.
Belgian Prime Minister Charles Michel tweeted: "Violence can never be the answer! We condemn all forms of violence and reaffirm our call for political dialogue."
Around 70 polling stations had been raided by police, Spanish Interior Minister Juan Ignacio Zoido said.
The aim of the raids was to seize referendum material and not to target people wanting to vote, another senior government official said.
Spain's Deputy Prime Minister Soraya Saenz de Santamaria said police had acted in a proportionate manner.
"We have been made to do something we didn't want to do," said Enric Millo, the central government's representative in Catalonia, at a news conference.
A top-flight Spanish soccer match between Barcelona and Las Palmas on Sunday will be played without any supporters in the stadium because of the unrest, the Catalan club said.
"FC Barcelona condemns the events which have taken place in many parts of Catalonia today in order to prevent its citizens exercising their democratic right to free expression," a statement on the club's website said shortly before the game was scheduled to kick off.
One analyst said the scenes being played out across Catalonia on Sunday would make it harder for Madrid and Barcelona to find a way forward.
"I think it is going to make the clash more intense and make it more difficult to find a solution," said Antonio Barroso of Teneo Intelligence.
Puigdemont originally said that if the "yes" vote won, the Catalan government would declare independence within 48 hours, but regional leaders have since acknowledged Madrid's crackdown has undermined the vote.
Markets have reacted cautiously but calmly to the situation so far, though credit rating agency S&P said on Friday that protracted tensions in Catalonia could hurt Spain's economic outlook. The region accounts for about a fifth of the economy.
(Additional reporting by Angus Berwick in Sant Pere de Torello, and Adrian Croft and Sonya Dowsett in Madrid; Writing by Sonya Dowsett and Pravin Char; Editing by Janet Lawrence)
(Except for the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)