Data from the country's national registry office on Sunday shows his rival, the leftist Ivan Cepeda, was some 368,000 votes behind with 48.4 per cent.
De La Espriella, 47, has proposed a tough crackdown on crime, as well as the end to peace talks with armed groups and a boost to Colombia's oil and gas sector.
Cepeda, 63, has vowed to continue the policies of President Gustavo Petro, a former rebel and the country's first leftist president, which include state pension payments for the poor, union-backed labour reforms, peace talks with armed groups that have fought the state for decades and a moratorium on new oil projects.
De La Espriella blames Petro for the country's economic and security woes and has vowed to lower taxes and reduce the size of the state by up to 40 per cent, but has said he will preserve Petro's 23 per cent increase in the minimum wage, along with other popular social measures.
Whoever wins will grapple with high public debt and a divided Congress, which could stymie reform proposals.
Some 400,000 voters turned in blank ballots, usually seen as a protest vote.