The seven-time Ballon d'Or winner put pen-to-paper on a two-and-a-half-year deal at David Beckham's Inter Miami, bringing an end to his time in European football.
Messi was serenaded by rain-soaked fans as he walked out in front of a 20,000-strong crowd DRV PNK Stadium.
And some of the biggest names in US sport and music have combined to create a welcome video for the Argentine as he begins his new adventure in MLS.
Among the first to welcome Messi's arrival was seven-time Super Bowl winner Tom Brady, who retired from the NFL earlier this year.
"Leo, I wanted to say congratulations on the big move to Miami," said the 45-year-old.
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Four-time NBA champion Steph Curry also gave his best wishes to Messi saying: "I just want to say congratulations on the transition. Good luck, I know it's new beginnings."
US Men's national team head coach Gregg Berhalter added: "I want to welcome you to Miami and the United States."
From the world of music, American DJ and record producer DJ Khaled said: "Messi, we love you, welcome to Miami Dade County 305. Welcome brother, we love you.
Meanwhile, Latin pop legend Gloria Estefan and husband Emilio said: "Messi, welcome to Miami, you'll bring a lot of pride and unity to south Florida."
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Inter Miami posted the video clip on Tuesday evening alongside the caption: "To new beginnings. A special welcome for Leo to our city!"
Messi is set to make his eagerly-awaited debut against Mexican side Cruz Azul in the first round of the 2023 Leagues Cup on Friday.
Tickets have reportedly been exchanging hands for a reported £84,000, as fans scramble to get their first sighting of Messi in an Inter Miami shirt.
Messi will be joined at the club by former teammate Sergio Busquets in what amounts to an incredible double coup for Miami and MLS.
But both stars will need to instantly inject their magic into a flailing Inter Miami side who find themselves rock bottom of the Eastern Conference with just 18 points from 22 games this season.