In unusually tense confrontations, protesters threw cans, stones and flares at riot police, and set garbage containers and cardboard on fire in the middle of several central Barcelona streets, including a thoroughfare housing designer stores and the local stock exchange, according to Reuters witnesses.
Fences were on fire next to La Pedrera, one of Catalan architect Antoni Gaudi's most famous buildings and one of the city's main tourist attractions.
Police charged several times through the crowd with batons. A spokesman for the regional Mossos police said they were trying to make space around the local headquarters of the Spanish government. Four people were detained, the spokesman said.
Reuters reporters saw police fire foam projectiles at the protesters. They also witnessed Spanish national police firing blanks in the air from rubber bullet guns. Police could not immediately be reached for comment.
Catalan government spokeswoman Meritxell Budo, speaking on Spanish national broadcaster TVE said separatists have proven they are peaceful and only an isolated group behaved violently, sullying their reputation.
"The regional government condemns all violent actions as we always have done," she said.
Catalan separatism has long prided itself on being a peaceful movement and its leaders say that has not changed.
But there were concerns in Madrid that heavy jail sentences for the separatist leaders could unleash pent-up frustration among a radicalized fringe, a senior parliamentary source told Reuters last week.
Police also charged protesters in the cities of Girona and Tarragona, TV footage showed. Catalan police warned people on Twitter not to approach the epicenter of protests in Barcelona and Girona for safety reasons.
The leader of Spain's center-right Popular Party, Pablo Casado, on Twitter called for acting Prime Minister Pedro Sanchez to activate the national security law and take control of Catalonia's security forces to "guarantee security and public order."
In a statement, Spain's acting government said it will guarantee security in the region, without elaborating further.
"A minority is trying to impose violence in the streets of Catalan cities," the statement said, praising coordination between regional and national police.
Thousands of demonstrators had taken to the streets of the regional capital earlier in the evening. Some lit candles and chanted "Freedom for political prisoners."
Pro-independence leaders have vowed to keep pushing for a new referendum on secession, saying Monday's prison sentences strengthened the movement.
Oriol Junqueras, who was given the longest sentence of 13 years for his role in organizing the 2017 referendum which was ruled illegal, told Reuters in his first interview after the sentence that it would only galvanize the independence movement.
"We're not going to stop thinking what we think, ideals can't be derailed by (jail) sentences," he said, adding that a new plebiscite was "inevitable."
Demonstrators had blocked railways on Monday and thousands descended on Barcelona's international airport, where some clashed with police. An airport spokesman said 110 flights were canceled on Monday and a 45 more were canceled on Tuesday.
Two years after the debacle of the first plebiscite, Catalonia's independence drive still dominates much of Spain's fractured political debate, and will likely color a national election on Nov. 10, Spain's fourth in as many years.
Spain's main parties have consistently refused to hold an independence referendum in Catalonia, although the acting Socialist government says it is open to dialog on other issues.
Diana Riba, wife of convicted leader Raul Romeva, told Reuters the independence drive would prevail over time.
"This is a very long process, but we will see results as we did with the feminist movement, how they grew until becoming massive and achieving the rights that they were seeking," she said, calling for "everyone to take to the streets."