The long-awaited ruling capped weeks of rising tension, and puts the Catalan question at the heart of the political debate less than a month before Spain heads into its fourth general election in as many years, AFP reported.
The 12 defendants were put on trial in February for their role in the banned October 1, 2017 referendum and the short-lived independence declaration that followed it.
The harshest sentence of 13 years was handed to former Catalan vice president Oriol Junqueras who served as the main defendant in absence of Carles Puigdemont, the region's leader who fled Spain to avoid prosecution.
In a tweet from Brussels, Puigdemont denounced the sentences as an "outrage".
"100 years in all. An outrage. Now more than ever, by your side and those of your families. It is time to react as never before," he wrote.
And in a letter to his supporters released on Monday, Junqueras said the story was far from over.
"Nothing ends today, you neither win nor convince," he wrote in remarks directed at Spain's central government.
"We will come back even stronger... and win.
Spain's government has expressed hope that the trial's end would allow it to move on from the crisis in the wealthy northeastern region, where support for independence had been gaining momentum over the past decade.
"Following the Supreme Court decision we need to turn the page based on peaceful co-existence in Catalonia through dialogue," Spanish Prime Minister Pedro Sanchez said, speaking in English.
But Junqueras' leftwing ERC party has said dialogue would not be possible without an "amnesty" for "political prisoners and those in exile".
Barcelona Football Club also tweeted its own response to the ruling, saying: "Prison is not the solution.
"The resolution of the conflict in Catalonia must come exclusively from political dialogue."
The separatist movement is hoping the guilty verdicts will unite their divided ranks and bring supporters onto the streets.
In the coming days, demonstrators will march from five towns towards Barcelona where they will congregate on Friday, when a general strike has been called.
For many, the situation has brought back memories of tensions in the street in the run-up to the October 1, 2017 referendum which was marred by police violence, and ahead of the short-lived independence declaration that followed on October 27.
Former parliamentary speaker Carme Forcadell was handed 11 years and six months in prison, while five other former ministers were jailed for between 10 years and six months and 12 years.
Two influential Catalan civic leaders, Jordi Sanchez and Jordi Cuixart, were sentenced to nine years in prison, while the remaining three leaders escaped jail time and were each handed a fine of around 60,000 euros ($70,000).