Voters overwhelmingly approved a blueprint for change that conservatives fear could be taken up by other regions and leave Spain's government cash-strapped and weak.
Some opponents of increased autonomy for Catalonia fear it will lead to a violent break up of Spain, but supporters say it might help the national government in peace talks with separatists in the neighbouring Basque country.
Nearly three out of four voters said 'yes' to the plan in a referendum.
But a low turnout immediately raised questions about its validity.
According to official data, with 98.5 per cent of the votes counted, 73.9 per cent of Catalans voted in favour.
But just under half of the five million Catalans eligible to vote actually did so, with 50.6 per cent staying away from the ballot box.
More than five per cent of ballot papers were blank or void.
The referendum asked the wealthy north-east region of Catalonia, which includes the city of Barcelona, to decide on a text giving it greater control over raising taxes and judicial affairs.
The autonomy text also promotes a wider usage of the Catalan language and gives the region increased say on foreign affairs and control over non-strategic airports and ports.
PM hails support
Spain's Socialist Prime Minister Jose Luis Rodriguez Zapatero hailed the "large support" shown by voters for the text.
Catalonians have "spoken clearly" and "in a very large majority" in favour of greater autonomy, he said.
The autonomy charter would bring "greater recognition of the identity" of the region, he added.
The referendum was seen as a crucial test for Mr Zapatero as he seeks to rally support for peace talks with separatists demanding self-rule for the Basque region of Spain.
Before casting his vote, the Catalonia regional government's President Pasqual Maragall said the referendum was "the most important day since the constitution was signed in 1978 and (Catalonia's) first statute", in 1979, during Spain's transition to democracy after decades of dictatorship under Franco.
Mr Zapatero has weighed in heavily in support of the autonomy charter and became personally involved in working out a compromise in the Spanish parliament and in the subsequent political campaigning.
Together with the Basque question, the Catalonia vote has become one of the most perilous political issues of his time in power.
Opposition to the charter also came from separatists in the territory.
The Catalan separatist ERC party argued the text did not go far enough, and has demanded that Catalonia be recognised as a nation.