The Mexican president has sent a letter to Spain’s King Felipe VI and Pope Francis urging them to apologise for human rights abuses committed during the conquest of the region.
Andrés Manuel López Obrador said the indigenous peoples of Mexico had been the victims of massacres.
In a video filmed at the ruins of an ancient Mexican city , he called for a full account of the abuses.
“The time has come to reconcile. But let us ask forgiveness first,” he said.
‘The sword and the cross’
Mr López Obrador was unsparing in his criticism of both Spain and the Vatican.
“There were massacres and oppression. The so-called conquest was waged with the sword and the cross,” he said.
“They built their churches on top of the (indigenous) temples.”
Mexico has the world’s second biggest Roman Catholic population, after Brazil.
The government in Madrid responded quickly, firmly rejecting his request for an apology.
“The arrival, 500 years ago, of Spaniards to present Mexican territory cannot be judged in the light of contemporary considerations,” Spain said in a statement.
“Our two brother nations have always known how to read our shared past without anger and with a constructive perspective,” it added.
Aztec Empire defeated
The Spanish conquest of the Americas began with the arrival of an expedition led by Christopher Columbus in 1492.
Conquest of Mexico began when a small army led by Hernán Cortés, landed in modern-day Veracruz state in 1519.
The powerful Aztec Empire was eventually defeated, marking the beginning of 300 years of Spanish rule.
Mexico gained independence after a war that lasted from 1810 to 1821 and became a federal republic in 1824.
Mr López Obrador came to power in December, with a left-wing agenda.
He promised to tackle corruption, reduce inequality and lift millions of Mexicans out of poverty.
Relations with Spain’s centre-right government have been friendly so far.