Grand Mosque President Dalil Boubakeur said the wall and door of the religious site was desecrated overnight Monday with an inscription "insulting to Muslims and Islam," the daily Ouest France reported.
"We deeply deplore the racist violence and hostility shown against the iconic institution of Islam in France that is the Mosque of Paris," he said in a statement.
Boubakeur indicated he had filed a complaint with the police commissioner of Paris' 5th arrondissement.
Abdallah Zekri, president of the French National Observatory Against Islamophobia, also condemned what he called a "heinous act."
Zekri's own residence in Nimes, France, was defaced by neo-Nazi and anti-Islamic graffiti last month.
Meanwhile, Paris Mayor Bertrand Delanoe issued a statement expressing his "indignation and anger," adding, "tags that are abusive ... are both irresponsible and unacceptable."
The Grand Mosque was the scene of a call for religious tolerance during the Muslim Eid celebrations last month, when French Prime Minister Jean-Marc Ayrault visited it to denounce Islamophobic acts.
"I know the concerns you have when the faithful are the target of discrimination and the freedom to practice his religion is threatened," he said. "Also, I want to assure you of the government's determination to uphold the freedom of conscience and freedom of worship, which are among the foundations of our nation.
"I repeat emphatically: Any interference with the free exercise of religion is intolerable, and all faiths must speak in our country in accordance with the laws of the Republic, secularism and beliefs," the PM declared.
Targeting a racial group for religious defamation is a crime punishable by a year in prison and a $60,000 fine under French law.
But despite the prohibitions, 201 such acts were recorded by the French anti-Islamophobia group in 2012 -- an increase of 28 percent over the previous year, the Algerian news agency APS reported.
Last week, police in the in the northern French city of Hazebrouck said two pig heads were found at the site of the future mosque there. No charges have been filed, but an investigation was under way, France3 reported.
Deputy Hazebrouck Mayor Jean-Pierre Allossery wrote in a local newspaper column the incident was at best the "stupidity of clueless person" and at worst a "deliberate act [that is] very bad for democracy."
A similar incident happened Nov. 8 in Amboise, France, where a pig's skull was found by workers on the site of a future Turkish cultural center.
"I condemn this act, but also the politicians who do not take action," Turkish Cultural Association official Kazim Hofflu told the France Bleu radio network.
It was the third such incident at the site in the central France department of Indre et Loire. A complaint was also filed in 2012 after the discovery of a boar's head on the same site.
"It is shocking that the mayor, elected officials, the police of Indre et Loire do not react," a Turkish community official told the broadcaster. "It will not be a mosque -- just a cultural center. It is important for the city of Amboise, since between 20 and 30 percent of the population is Muslim."