The 11th-hour omission could clear the way for two-time Socceroo Jacob Italiano to continue impressing coach Tony Popovic in the race for the right-back vacancy.
Croatian-based Karacic reported to Socceroos camp for the friendlies against Cameroon this Friday and Curacao on Tuesday, only to be sent home once he was unable to shake a persistent foot injury.
It's the latest setback for the 29-year-old, who withdrew from friendlies against Canada and the USA in October for medical reasons.
Popovic conceded the timing of the latest incident was especially poor, with Australia playing its last two matches before flying to North America for the World Cup that begins in June.
"It's actually the third time it's happened to him," Popovic said of Karacic's late withdrawal.
"It's always disappointing for the player, the World Cup is so close. It was an opportunity for him to show himself.
"Obviously he wanted to be a part of it and wanted to push through the pain but he was restricted, and we've got to look after the player as well."
Popovic intimated Karacic's high workload at Croatian club NK Osijek had not helped his chances of being fit for the crucial friendlies.
"We obviously have our thoughts on what we believe is best for him to do now when he gets back," he said.
"But he also has the pressures of playing. He's at a club that's trying to avoid relegation, he's playing very well for them. So we can understand the club's point of view."
Kye Rowles will join Popovic's squad for the March friendlies, but specialist right-back Italiano looks likelier to play big minutes in Karacic's sudden absence.
Karacic, Italiano and Jason Geria appear front-runners to fill the right-back spot usually occupied by Blackburn Rovers' Lewis Miller, who will miss the World Cup with his Achilles injury.
Italiano made his Socceroos debut in October 2025 - coincidentally replacing Karacic in the squad - and has been excelling for Austrian side Grazer AK since recovering from a calf injury in February.
Popovic said there was now an especially big opportunity in front of the 24-year-old.
"He's had a couple of solid games, scored a hat-trick (earlier this month) so he's full of confidence," Popovic said.
"I'd love to find another Jacob Italiano, whether it's that position or another position, someone that can come through and surprise everyone and then continue on with some really good form at their club."
Popovic was less enthusiastic to hint at which player would slot into the vacancy at striker for the two friendlies.
Injuries to Mohamed Touré and Nicholas D'Agostino, and form concerns over Mitch Duke, have meant one of uncapped duo Deni Juric or Ante Suto could start against Cameroon in Sydney.
Popovic's mind has been made up for the Cameroon match ahead of Thursday's final training session on Accor Stadium, delayed by lightning in the area.
"Yes, we have (settled on a striker)," Popovic said.
"You'll see tomorrow. I'll let you enjoy that tomorrow when you see who's out there."
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