Messi scored twice from close range to maintain his 100 percent win record with Miami. It was a welcome change for the club who were winless in 11 league games before the World Cup winner's grand arrival.
The start of the match was delayed by 95 minutes because of a thunderstorm, but once the game got under way, Messi took little time to settle down and opened the scoring in the seventh minute.
The Argentine began his move at the half line and made a run into the box as Robert Taylor chipped the ball over. Messi intercepted and volleyed home from the edge of the six-yard box.
Orlando equalised 10 minutes later when Uruguayan midfielder Cesar Araujo pounced on a loose ball off a corner and fired it home, but Miami restored their advantage three minutes into the second half when Josef Martinez scored from the penalty spot.
Taylor and Martinez then combined in the 72nd minute on a counter-attack to set up Messi for another close-range volley and the unmarked Argentine made no mistake to beat Pedro Gallese in Orlando's goal.
Messi will now head on the road with Miami for the first time in Sunday's match with FC Dallas in Texas, which offers a place in the quarter-finals of the tournament for top flight teams from Major League Soccer and Mexico's Liga MX.
Another former Barcelona star Jordi Alba made his debut for Miami, coming on as a 64th minute substitute and although Araujo had an effort disallowed in stoppage time, there was little trouble in the latter stages for Messi's team.
Miami right-back DeAndre Yedlin said his team played with belief, thanks to the presence of the Argentine.
"He just gives everyone around him confidence. You can give him balls in difficult situations and know he's going to make something out of it.
"The flipside is that for the teams we're playing against, it puts a bit of fear in their eyes. They're dropping back on their heels a bit and that gives us more space to play," he said.