The independent candidate's withdrawal could give a small boost to her fellow conservative Ricardo Anaya, who is in second place for the July 1 vote, as he tries to pull off a come-from-behind win against the leftist front-runner, Andres Manuel Lopez Obrador.
But Zavala, 50, did not immediately endorse another candidate.
"I am withdrawing my candidacy in the interest of consistency, in the interest of political honesty, but also to free those who have so generously supported me so they can decide as they must in this difficult race," she told Mexican TV network Televisa.
Zavala, the wife of former president Felipe Calderon (2006-2012), was standing as an independent after resigning last year from the National Action Party (PAN), accusing Anaya, its then leader, of strongarming his way to the party's presidential nomination.
Anaya, who is running for a coalition between the PAN and two left-wing parties, sought to mend fences as Zavala announced her withdrawal.
She is "a brave woman of principle," he wrote on Twitter.
"Her contributions to the country and in particular this election campaign have been very valuable. All my recognition to her and her team."
Despite strong pre-campaign poll numbers, Zavala never gained momentum after the race officially opened on March 30.
The latest poll average from Mexican website Oraculus gave her 4.4 percent of the vote, leading only her fellow independent, governor Jaime "El Bronco" Rodriguez, with 2.6 percent.
Lopez Obrador has 43.4 percent, Anaya 29.3 percent and ruling-party candidate Jose Antonio Meade 20.2 percent, according to the site.
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