Catalonia's regional parliament has passed a motion saying it will establish an independent Catalan Republic.
Separatist legislators erupted in applause as the vote was approved with 70 votes in favour, 10 against and two blank ballots.
Most opposition members had left the chamber in protest moments before the vote.
No country has expressed support for the secession bid.
The motion in the Catalan parliament called for beginning an independence process that includes drafting Catalonia's new top laws and opening negotiations "on equal footing" with Spanish authorities to establish co-operation.
Spain's prime minister had earlier urged the Senate to grant special constitutional measures that would allow the central government to take control of Catalonia's autonomous powers to halt the independence bid.
Mariano Rajoy, who received rapturous applause before and after his impassioned speech in the Senate in Madrid, told the chamber Spain was facing a challenge not seen in its recent history.
What is happening in Catalonia is "a clear violation of the laws, of democracy, of the rights of all, and that has consequences", he said.
Mr Rajoy said the government's first move would be to dismiss Catalan President Carles Puigdemont and his regional ministers if the Senate approves the Spanish government's use of Article 155 of the constitution in a vote later on Friday.
The special measures, he said, were the only way out of the crisis, adding that Spain is not trying to take away liberties from Catalans but instead protect them.
Thousands of people watched the voting process and the counting live on big screens outside Catalonia's parliament in Barcelona, and cheered and danced after the motion was passed.
Mr Puigdemont and vice president Oriol Junqueras exchanged congratulatory embraces and handshakes after the vote.
The Spanish Senate has authorised the central government to take control of the region.
A majority of senators gave prime minister Mariano Rajoy the go-ahead to apply unprecedented measures including sacking Catalan President Carles Puigdemont and his cabinet.
It also authorised him to curtail Catalan parliamentary powers.
Mr Rajoy immediately called for calm, tweeting: "I call on all Spaniards to remain calm. The rule of law will restore legality to Catalonia."
