At 36-years-old, the Argentine was plying his trade back in his homeland after joining Estudiantes in January from Hebei China Fortune, but has now opted to stop playing after featuring in senior teams for 17 years.
Mascherano started his career at River before moving to Brazil with Corinthians.
However, it was a controversial transfer to West Ham in 2006 which put Mascherano truly into the public eye, particularly in Europe. Despite being one of the most sought-after young players in the world at the time, he and Carlos Tevez joined struggling West Ham in the Premier League.
Third-party ownership and other player ownership regulations ultimately overshadowed his work on the pitch, but he did do enough to earn a move to Liverpool in 2007.
Although he would win no major honours with the Reds under Rafa Benitez, he developed into one of the most tactically adept deep-lying central midfielders in Europe.
Barcelona eventually came calling, and he joined the Blaugrana for €24m in 2010.
His period at the Camp Nou will go down as the most successful part of his career as he won five La Liga titles, two Champions League titles, and five Spanish Cups in his time in Catalunya.
It was also during this time when he adapted to playing as a central defender under head coach Pep Guardiola, whose wish to play the ball out from the back saw the Argentine partner with Gerard Pique in the middle of the backline to much success.
His career wound down with a move to China before the eventual move to Estudiantes.
Post pandemic, I thought that I was going to feel the spark again, but the truth is that I could not.Javier Mascherano
Mascherano explained the reasons for his choice at a club press conference on Sunday.
"It is time to finish my career because of things that happened to me in recent months, that on a personal level and after having thought about it for all this time, the most correct thing is to finish today," he said.
"I have lived my profession 100 per cent, I gave the best I could and today I find that it has been difficult for me for a while and I do not want to disrespect Estudiantes, who trusted me to return to Argentina, or my colleagues, or this profession.
"It does not have to do with the club or with a result, but with feelings that one is feeling over recent times, which make the illusion that one had of being a footballer fade.
"Post pandemic, I thought that I was going to feel the spark again, but the truth is that I could not. Out of respect for everyone, it is time to step aside and end this race. I didn't want to let time go by.
"I am infinitely grateful to the clubs I played for, the team-mates I had throughout my career and to Estudiantes who gave me the opportunity to come and play in recent times. It was less than I expected, things happened this way and sometimes you don't choose the end.
"I thank [coach Leandro] Desabato, the institution and my colleagues for having put up with me this last time."