The World Cup-winning captain, who has a hamstring strain, stayed rooted to the bench throughout the 4-1 friendly win against a Hong Kong select XI.
It brought a show of anger from the near-capacity crowd of 38,323 who had paid upwards of 1,000 Hong Kong dollars (£100) to see their hero, and in many cases a lot more.
Halfway through the second half, chants of "We want Messi" rose around the Hong Kong Stadium from fans desperate to see the greatest footballer of his generation in the much-hyped exhibition game.
The booing became louder during the last 10 minutes when it became clear that the eight-time Ballon d'Or winner would not make even the briefest of cameos.
The jeers rose to a crescendo at the final whistle and Miami co-owner Beckham was drowned out by booing as he tried to thank the crowd for "their incredible support" while fans signalled their anger with thumbs-down gestures.
Miami co-owner Beckham was drowned out by booing as he tried to thank the crowd "for their incredible support" while fans signalled their anger with thumbs-down gestures.
"We understand the disappointment of the fans for the absence of Leo (Messi) and Luis Suarez," Miami coach Gerardo Martino told reporters, explaining the club's medical team had taken the decision after an assessment on Sunday morning.
"We understand a lot of fans are very disappointed and we ask for their forgiveness.
"We wish we could have sent Leo and Luis on for at least a while but the risk was too big."
The 36-year-old Messi played just six minutes in Miami's last match, in Saudi Arabia on Thursday, and now faces a race against time to be fit for the new MLS season which starts on February 21st.
Bitter end to 'Messi mania'
It was a bitter end to days of Hong Kong "Messi mania" in the lead-up to the match.
Tens of thousands turned up just to watch him train on Saturday, where he did little more than jog and stretch.
The team hotel was besieged by hundreds of fans trying to glimpse their hero, and a traditional junk boat was cruising around Victoria Harbour with Messi's face plastered across sails.
Messi shirts had been flying off the shelves after tickets for the match sold out in an hour when they went on sale in December.
Echoing the fans' anger, the Hong Kong government said they could withdraw their HK$16 million (£1.6 million) funding to the organisers that helped bring Inter Miami to the city.
"The Government, as well as all football fans, are extremely disappointed," it said in a statement.
"The organiser owes all football fans an explanation."
Miami's starting line-up featured neither of their other former Barcelona stars, Sergio Busquets, Jordi Alba or Luis Suarez.
Robert Taylor opened the scoring for the MLS side in the 40th minute with a delightful right-foot curling shot from the left-hand edge of the box.
Two minutes later Hong Kong's Henri Anier laced a left-foot finish home to make it 1-1.
Miami regained the lead after half-time when Lawson Sunderland found the target from close range and Leonardo Campana increased the lead in the 56th minute.
Busquets and Alba finally made an appearance from the bench after 62 minutes to a smattering of cheers before Ryan Sailor rounded off the scoring for Miami in the 85th minute with a glancing header.
It was Miami's first win in five matches on their globe-trotting pre-season tour.
They now move on to Japan for a friendly against Vissel Kobe on Wednesday before flying back to the United States.
