The protests, one of several in recent years meant to "protect" the National Electoral Institute (INE), come after Lopez Obrador sent a sweeping package of constitutional reforms to Congress, which would include an overhaul of the INE.
Organizers said 700,000 people turned out, which could mark one of the largest protests against Lopez Obrador as his administration comes to a close.
The Mexico City government, which is controlled by Lopez Obrador's MORENA party, said just 90,000 people attended. The disparity in counting turnout has also occurred at previous pro-INE demonstrations.
Lopez Obrador has made it no secret the package is meant to influence debate before June 2 voting in which his political successor Claudia Sheinbaum is likely to win, though the president has said it is unlikely most reforms will pass.
One would turn the INE into the National Institute of Elections and Consultations, which would take over the country's local electoral bodies and shrink the number of counselors heading the group. It would also require electoral judges be elected by popular vote.
"Authorities are seeking to eliminate (autonomous institutions), to subordinate them or take them over," Lorenzo Cordova, the former head of the INE, said to the crowd. "We've seen a ferocious attack against these institutions."
The president has long shared his dislike of the INE, including accusing the electoral body of helping to engineer his defeats when he ran for the presidency in 2006 and 2012.
Protesters on Sunday accused Lopez Obrador of meddling in an attempt to concentrate power in the hands of his party's government, though Lopez Obrador has said he will respect the results of the election.
Demonstrators also used the protests to speak out against other hallmarks of Lopez Obrador's administration, including what they allege is a failure to curb widespread violence and social spending programs.
"The current government is leading us to catastrophe," said Maria de los Angeles Lopez. "To be afraid of going out on the streets, to be afraid our money will no longer be enough, that is why I came out to protest."
(Reporting by Kylie Madry in Mexico CityAdditional reporting by Alberto Fajardo and Gloria Lopez for Reuters TVEditing by Chris Reese and Matthew Lewis)
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