The gathering is seen as the left-wing populist's riposte to opponents of a controversial new election law that he promoted.
The rally is Lopez Obrador's "response to the opposition coming out to protest against his electoral reform," political analyst Jose Antonio Crespo told AFP.
Tens of thousands of Mexicans demonstrated on February 26 against a new law reducing the size and budget of the National Electoral Institute (INE), the independent body that oversees elections.
Critics see the changes -- which were approved by the ruling party-controlled Congress last month -- as an attack on democracy ahead of the 2024 presidential election.
Mexican presidents are barred from serving more than one six-year term, and Lopez Obrador has ruled out trying to change the constitution to stay in office.
Even so, he is keen to see his Morena party hold onto power after he stands aside.
Lopez Obrador, who enjoys an approval rating of around 60 percent, has called Saturday's rally to coincide with the 85th anniversary of the nationalization of Mexican oil.
"We have to reaffirm our independence, our sovereignty," said the 69-year-old leader, whose nationalist energy policies have unsettled foreign governments and investors.
Political columnist Hernan Gomez Bruera described the electoral reform and oil expropriation anniversary as a "pretext" for the president to mobilize his supporters.
The rally is due to start at 5 pm (2300 GMT) and Lopez Obrador is expected to address the crowds in Mexico City's main square from the National Palace.
A similar rally in November drew hundreds of thousands of Lopez Obrador's supporters into the streets of Mexico City, two weeks after an earlier protest against his electoral reforms.
Lopez Obrador alleges that the INE endorsed fraud when he ran unsuccessfully for the presidency in 2006 and 2012, before winning in 2018.