Mascherano will coach his former Barcelona teammate Lionel Messi at the club and replaces Gerardo Martino, who stood down last week due to "personal reasons".
The 40-year-old has most recently worked as coach of the Argentine Under-20's and their Olympic team at the Paris Olympics.
He made 203 appearances for Barcelona and, as well as playing alongside Messi, he was a teammate of current Inter Miami players Jordi Alba, Sergio Busquets and Luis Suarez.
In his job with the Argentine FA's youth set-up, Mascherano coached Inter Miami's players Tomas Aviles, Facundo Farias and Federico Redondo.
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