No other Mexican player has won more titles and he is widely considered second only to Hugo Sanchez as the country's best player ever.
Now 38 and still scoring goals, "Rafa", as he is known to fans, was one of a generation of Mexican players hailed as "boy heroes" in the 1990s.
He made his professional debut in 1996 – not long before Sanchez's retirement – with Atlas de Guadalajara and first played for the national team the following year.
While playing for Mexico against Chile in a Copa America game in 1999, he caught the eye of a scout for French side AC Monaco.
"I went to the Copa America to see a Chilean player. But I spotted a defender in the Mexican side that I liked," said scout Julien Muller.
Thus began Marquez's march to the top flight of European football, leading to two Champions League titles with Barcelona.
"I have great memories of the Copa America. The first one I played in gave me the chance to make myself known and to go to Europe," he said in 2015.
His first 11-year spell in Europe included a victory with Barcelona in the Champions League final against Arsenal in 2006.
He returned briefly to Europe in the 2014-2015 season to play for Hellas Verona in Italy.
He later played for the New York Red Bulls and then for Leon in Mexico, winning a league title, before returning in 2016 to Atlas, where he still plays.
"Having Rafael Marquez on the team is amazing," said Atlas Argentine defender Facundo Erpen.
"He is an open book to everyone. Anyone can ask him things and learn from him constantly."
Marquez has captained Mexico in four World Cups. Still potent despite injuries, he scored the winning goal in the 89th minute of a 2-1 World Cup qualifier victory over the United States last November.
Mexico's current coach, Juan Carlos Osorio of Colombia, had said recently that he intended to take Marquez to next year's World Cup in Russia.
"We hope that Rafael is still fit" for that challenge, he said.
Scandal struck on Wednesday however when the US Treasury accused Marquez of being a "front person" for a major drug trafficking ring.
He was one of 22 people and 43 entities the Treasury placed on a sanctions list in relation to a Guadalajara-based cartel.
The Treasury said Marquez has a "longstanding relationship" with cartel boss Raul Flores Hernandez and held assets on his drug cartel's behalf.
Marquez was the top trending topic in Mexico on Twitter on Wednesday.
The country is used to news of violence and corruption related to its powerful drug gangs.
But football fans expressed shock and disbelief at Wednesday's news about their sporting hero.
"This is really bad, because he is a role model for children," said Fernando, a young man in a Barcelona shirt.
Another fan in the streets of Mexico City, shoeshine man Mario Rodriguez, said the allegation was "absurd, nonsense."
One of Marquez's co-accused, well-known Mexican singer Julion Alvarez, rushed to the defense of his "great friend."
"He's got one of the longest careers in football. Do you really think he would need to do something like this?" he said in a video posted on Facebook.