BARRIO (BBC) – With just over a quarter of votes counted, Ms Machado had 93%, even though she is currently barred from holding office.
The other nine candidates are trailing far behind the 56-year-old Ms Machado.
The winner will run against the government candidate.
The opposition, which has historically been deeply divided, called the primary – in which ordinary people were allowed to vote – to close ranks behind a single contender for the presidency.
The governing PSUV party has not yet announced who its candidate will be but it is widely expected to be President Nicolás Maduro, who has been in power since 2013.
While most opposition parties boycotted the last presidential election after some of their candidates were jailed or barred from running, they have decided to take part in the 2024 poll, even though they say the odds are stacked against them.
It is unclear at present whether the ban on María Corina Machado will be lifted before the election.
It was imposed this June by the comptroller general at the time, Elvis Amoroso, who is a close ally of President Maduro.
Mr Amoroso barred Ms Machado from public office for 15 years alleging corruption without offering any proof.
There has since been huge pressure on the government to reverse that ban, not least from the United States.
The US last week eased some of the sanctions it had imposed on Venezuela’s oil and gas industry following a deal between Venezuelan government and opposition representatives to have the 2024 election monitored by international observers.
The deal stipulates that “the registration of all candidates that fulfil the constitutional requirement will be permitted”.
But immediately after it was signed, government negotiator Jorge Rodríguez said this did not apply to candidates who had already been barred by the comptroller general.
US Secretary of State Antony Blinken warned US sanctions could be reapplied if the Maduro government did not begin to lift the bans on opposition candidates by the end of November.
Ms Machado’s position has been strengthened by the high turnout at the primary, which the opposition organised without any help from the National Electoral Council.
There were long queues at the thousands of polling centres the opposition set up across Venezuela and also in major cities abroad.
Many voters said there was an atmosphere of hope and celebration as they cast their ballots.
The vote count was delayed by an internet server blockage but the first set of results gave María Corina Machado such an advantage that she declared victory.
“From tonight we begin a great movement for a great national alliance for the transformation of Venezuela,” she said.
“Today I received a mandate and I accept with Venezuelans the commitment of making that mandate matter,” she added.