Secessionist parties in the wealthy, northeastern region approved a plan to achieve independence by next year after winning a clear majority in 2015 regional elections, but ideological differences have hindered progress.
"We will look for an agreement (with the central government) until the very end, we will at every moment work with the will to hold a referendum in agreement with the state," Carles Puigdemont told regional lawmakers.
"But if we reach the end of our term in office and there has been no positive response, we will be ready to... call a referendum for the second half of September of next year."
Puigdemont was speaking ahead of a vote of confidence in his government that takes place Thursday.
He was forced to call the vote after his pro-independence coalition that rules Catalonia broke down in June when its most radical component - the far-left CUP party - refused to back the government budget for 2016.
The CUP had since said it would help bring the coalition back together again and vote for Puigdemont, but only in exchange for a Scotland-style referendum next year.
As such, Puigdemont had widely been expected to announce such a vote and lay out plans for his region's secession from Spain in his Wednesday speech.
"At the end of June next year, parliament will approve the necessary laws for Catalonia to be able to function as an independent state," he said.
After that, he added, citizens would be called to the ballot box for the referendum.
Catalan separatists have for years tried - in vain - to win approval from Spain's central government to hold an independence referendum like Britain's Scottish referendum in 2014 which resulted in a "no" vote.
Puigdemont's predecessor Artur Mas had already tried to hold such a vote.
But when it was banned by Spain's Constitutional Court, he held a symbolic independence vote in November 2014.
Over 80 percent cast their ballot in favour of independence then - although just 2.3 million people out of a total of 6.3 million eligible voters took part.
Unlike British former counterpart David Cameron with Scotland, which did get a vote in 2014, acting Prime Minister Mariano Rajoy has always categorically refused a referendum.
But as Spain remains mired in nine months of political stalemate after two inconclusive elections, it is not certain that Rajoy will still be in power next year.
Rajoy's traditional Socialist rivals however also refuse to back any referendum, so would not be any more flexible if they came to power.
The only party on the national scene that has said it would allow one is far-left, anti-austerity Podemos, but it does not have enough parliamentary seats to govern alone.
Catalans have nurtured a separate identity for centuries, but an independence movement surged recently as many became disillusioned with limitations on the autonomy they gained since the late 1970s after the Francisco Franco dictatorship, which had suppressed Catalan nationalism.
By Daniel Bosque / AFP