Despite falling behind in the 30th minute, the hosts managed to claim a comfortable victory in Saturday's clash at Chase Stadium.
Messi teed up Matias Rojas for Inter Miami's 48th-minute equaliser, before he put his own name on the scoresheet to turn the game in the home side's favour.
The Argentine produced an exquisite through ball to present Rojas with the chance to slot home Inter Miami's third goal of the evening.
Messi then rolled back the years to link up with his former Barcelona teammate Luis Suarez, providing all three assists in the Uruguayan's 13-minute hat-trick.
Messi makes historyFormer RB Leipzig attacker Emil Forsberg netted a late consolation for the visitors, but his penalty could not detract from a record-breaking night for Messi.
After being involved in all six of Inter Miami's goals, Messi registered six goal contributions in a game for the first time for club or country.
The 2022 World Cup winner also provided five assists in a single match for the first time in his career, taking his overall total for the season to 12 goals and 11 assists in 11 competitive appearances.
The Argentina international has now racked up 23 goals and 16 assists in 25 matches since he joined the American club last summer.
Inter Miami leading the wayLike Messi, Suarez also enjoyed a memorable night, registering his 31st career hat-trick and his first three-goal haul since arriving from Gremio earlier this year.
The Uruguayan forward has scored 12 goals and contributed seven assists in his 15 competitive matches for Tata Martino's side.
As a result of Messi and Suarez's exploits, Inter Miami have registered 32 goals in 12 MLS
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