After a lengthy delay due to adverse weather conditions in Florida, the 36-year-old quickly made up for the lost time.
Finland international Ryan Taylor expertly found Messi inside the box at the DRN PNK Stadium with a lofted through ball.
And the 2022 World Cup winner made no mistake from close range after finding himself unmarked.
He chested the ball down before hammering home a volley beyond goalkeeper Drake Callender.
It sparked jubilant scenes from the fans and players, with Messi grabbing his fourth goal for Inter in just his third outing.
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Though unlike his previous match against Atlanta United, there was no 'hold my beer' celebration.
But his celebrations were short-lived, as the visitors equalised in the 17th minute through Cesar Araujo.
Messi then thought he had grabbed his second of the match just after the half-hour mark after jinxing his way into the box.
However his effort smashed against the post to leave the forward with his head in his hands.
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It capped an eventful start to the game after the clash was delayed by over 90 minutes.
Torrential rain had waterlogged the pitch, while lightning in the area forced the players into the dressing room.