There were sporadic outbreaks of violence during the vote
Bolivian President Evo Morales has rejected an autonomy vote by the resource-rich Santa Cruz region, saying the unofficial referendum was illegal.
But he also called for dialogue with opposition governors, as three other states prepare for autonomy votes.
Partial results from Santa Cruz suggest more than 80% of voters backed plans to give their region more powers.
The poll pitted the region's mixed-race elite against the president's indigenous supporters.
An official count of 22% of the ballots showed 82% had voted to give the region more control over its resources, the AFP news agency reported.
The vote triggered noisy celebrations in Santa Cruz.
The region's Governor, Ruben Costas, called the result "the most important act of our republican history".
"You all with your vote have consolidated the beginning of the most important structural reform of our country," he said.
But in a national address after voting had finished, Mr Morales stressed the high levels of abstention - and called for opposition state governors to engage in dialogue with the government.
The president said he would ignore the results.
"This illegal and unconstitutional vote didn't have the success hoped for by certain families," he said, referring to landowners from Santa Cruz who helped organise the poll.
Many in Santa Cruz are critical of Bolivia's left-wing president.
He wants the country's wealthier eastern regions to contribute more to the poorer west, where the bulk of his indigenous supporters come from.
Mr Morales has promised radical reforms that he hopes will lead Bolivia, the poorest country in South America, out of poverty.
Leaders in Santa Cruz - home to about 25% of Bolivia's population - have demanded more local control over their resources.
They feel threatened by a draft constitution that proposes to limit large land holdings.
The proposals voted on in Sunday's poll include giving Santa Cruz more control over land distribution - and rich oil and gas reserves.
They also provide for the creation of a local police force.
Much of Sunday's voting was calm, but violence broke out in poorer areas as supporters of Mr Morales burnt ballot papers and ransacked polling stations.
One polling station was reported to have been destroyed, while elsewhere opponents of the referendum threw stones and clashed with those wanting to vote.
At least 20 people were injured, officials said, and unconfirmed reports said one man had died as police fired tear gas into a crowd.
The BBC's South America correspondent, Daniel Schweimler, said the result was always going to be in favour of greater autonomy since the opposition had said they would boycott the vote.
The question, our correspondent adds, is what happens next. Three other eastern provinces have said they too will vote on greater autonomy.