Mascherano has been named as Inter Miami's fourth permanent head coach after Tata Martino left his role due to personal reasons.
Martino led the club to the 2024 Supporters' Shield with a record-breaking points total, but he was unable to enjoy similar success in the postseason.
Inter Miami lost 2-1 in their three-game series against Atlanta United in the first round of the playoffs, bringing an abrupt end to their 2024 campaign.
Mascherano will now be tasked with leading Inter Miami to MLS Cup glory in 2025, as he links back up with his former Barcelona and Argentina teammate, Lionel Messi.
Beckham welcomes Mascherano to Inter Miami
The 40-year-old will also reunite with the former Barcelona trio of Jordi Alba, Sergio Busquets, and Luis Suarez.
Mascherano told Inter Miami's official website: "To be able to lead a club like Inter Miami is an honour for me, and a privilege I will strive to make the most of. I was drawn to the organization's undeniable ambition, and the infrastructure it has to support it.
"I'm looking forward to working with the people at Inter Miami to help the club reach new heights, and to give the fans more unforgettable moments."
Inter Miami co-owner David Beckham has expressed his delight at appointing the two-time Champions League winner as the club's latest manager.
Beckham said: "Throughout his career as one of the world's best players and as an experienced coach, Javier has always demonstrated what makes him great - relentless determination with the knowledge, instincts and understanding to back it up. We're very excited to welcome him to lead our team."
Mascherano's coaching history
Mascherano played for River Plate, Corinthians, West Ham United and Liverpool, before he moved to Barcelona to experience the most successful period of his playing career.
The midfielder-turned-central defender won 19 trophies during his time with the Catalan giants, including two FIFA Club World Cups, which is a competition he will get to experience as a manager when Inter Miami features in the newly expanded tournament in 2025.
Mascherano wrapped up his playing career with Hebei China Fortune and Estudiantes, before he was appointed Argentina Under-20 manager in December 2021.
The former Liverpool man took the Under-20 team to three tournaments, overseeing group-stage exits at the 2022 South American Games and the 2023 Under-20 South American Championship as well as a quarter-final appearance at the Under-20 World Cup in 2023.
Mascherano also combined his role with the manager of the Under-23 team for the recent Olympic cycle, helping his country qualify for the 2024 games, only to see his team eliminated by hosts France in the last eight.
After gaining valuable experience, Mascherano evidently feels it is the right time to leave his role with the Argentina Under-20 side to take on his first job in senior management.
Mascherano will be able to use the winter to get used to his new surroundings, before the 2025 MLS season kicks off in late February.