As one of Mexico’s most popular politicians, Mr Lopez Obrador is ranked in opinion polls ahead of the candidate supported by incumbent President Vicente Fox and his National Action Party (PAN) in the 2006 presidential poll.
The mayor was forced out of his job after Congress stripped his parliamentary immunity on April 7 to face prosecution for defying a court order after he condemned private land to build a public road.
The mayor claims the move was to stop him running in next year’s election.
Protest organisers estimated more than one million people jammed Mexico City’s Zocalo plaza and its adjoining streets in the “March of Silence.”
Federal officials said the numbers were much less.
The mayor’s supporters held placards saying “Fighting for Hope,” and “Lopez Obrador: 2006.”
The march was also supported by lawmakers of the mayor’s own Democratic Revolutionary Party (PRD).
Mr Lopez Obrador had difficulty reaching the podium to address his supporters because of the massive crowd.
Politicians from Mexico’s two main parties, the Institutional Revolutionary Party (PRI) and Fox’s PAN voted to strip Mr Lopez Obrador’s immunity so that he could be prosecuted for disobeying the court order.
If prosecuted, under Mexican law Mr Lopez Obrador cannot run for the presidency.
Prosecutors had warned him to abandon his job as mayor, saying that without immunity he was ineligible to hold the post.
But legal experts and politicians have argued over whether withdrawing his immunity from prosecution automatically ousts him from city hall.
“Tomorrow (Monday) I return to work in my office,” he told his crowds of supporters.
On Friday, a judge turned down on a technicality a prosecutor’s request to arrest Mr Lopez Obrador.