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The always dependable defensive midfielder was a crucial part of Argentina's best campaign at the tournament since 1990, not missing a minute of playing time as 'La Albiceleste' reached the final in Brazil after wins over Switzerland, Belgium and the Netherlands in the knockout stages.
Boasting a lethal attack with the likes of Sergio Aguero, Gonzalo Higuain, Angel Di Maria and arguably the game's greatest ever player in Lionel Messi, with Mascherano controlling the game from midfield, Alejandro Sabella's side looked to have the tools needed to lift the coveted trophy again.
Unfortunately, it wasn't to be, as a decisive extra-time strike from substitute Mario Götze gave Germany ultimate glory after a tense 90 minutes of regulation had Mascherano and Argentina right in the game.
While the outcome didn't go as planned, Mascherano still remembers the occasion fondly as the biggest moment of his career, despite winning multiple UEFA Champions league titles with Barcelona.
"For any footballer, playing in the World Cup is the ultimate dream," Mascherano said during the latest episode of the FIFA World Cup Magazine Show.
"Being able to play in a World Cup final is an incredible memory.
"Every player dreams of playing the most important match of their career, and there is no game more important for a footballer than a World Cup game, playing for their country.
The now-37-year-old played in one more tournament, the 2018 edition in Russia, before hanging up his boots in 2020 with 147 total caps for Argentina. He now coaches the Argentina U20s side.
The latest episode of the FIFA World Cup Qatar 2022 Magazine Show airs this Saturday, March 12 at 3:00pm (AEDT) on SBS or catch up via SBS On Demand.