Manzo, 40, was shot dead on Saturday during a Day of the Dead candlelight event in central Uruapan, in the violence-stricken western state of Michoacan.
Mexico’s security ministry said two suspects were arrested and a third was killed.
Sheinbaum convened an emergency meeting of her security cabinet on Sunday and condemned the “vile” assassination in a post on X.
“We reaffirm our commitment to deploy all the State’s efforts to achieve peace and security with zero impunity and full justice,” Sheinbaum wrote.
A march was planned for Sunday in Michoacan’s capital, Morelia, demanding justice and an end to violence and corruption.
Manzo, one of the few independent politicians in Mexico, had served as Uruapan’s mayor since September 2024.
Often seen wearing a bulletproof vest, he had urged the federal government to act more decisively against organized crime and publicly expressed fears for his safety.
“I don’t want to be just another mayor on the list of those executed,” he told journalist Joaquin Lopez-Doriga in September.
Uruapan, known as Mexico’s avocado capital, lies at the center of Michoacan’s booming avocado industry — a sector increasingly targeted by criminal groups amid rising US demand.
Several politicians, including other mayors and journalists, have been killed across Mexico in recent years.
“How many mayors haven’t they killed because they opposed making these pacts with organized crime?” Manzo asked in a September interview with Milenio TV.
He had appealed to Sheinbaum for stronger security and highlighted Uruapan’s economic significance ahead of a review of Mexico’s trade pact with the United States and Canada.
Manzo also urged greater action from Security Minister Omar Harfuch.
“Minister Omar Harfuch, help us,” he said in the same interview.
Harfuch said on Sunday that Manzo had received federal protection since December 2024, which was reinforced in May, including 14 National Guard troops providing perimeter security and local police handling immediate protection.
“The aggressors took advantage of the vulnerability of a public event,” Harfuch said. “Be certain that there will be no impunity.”