Amid a shortage of first-choice defenders, including Harry Souttar, Alessandro Circati and Jordy Bos, Popovic has had to delve deep into the Socceroos' depth chart ahead of next Thursday's clash with Indonesia in Sydney.
As well as recalling Davidson and Karacic for the first time since 2022, there also potential debuts for Sydney FC centre back Alex Grant and Melbourne City defender Kai Trewin.
Hibernian star Nectar Triantis, who can play in both defence and midfield, is also in line for his first senior appearance alongside Melbourne Victory's Ryan Teague.
While Davidson and Karacic offer tried and tested options, Popovic has taken his biggest gambles in the frontline.
The decision to axe Duke - one of Australia's most reliable, industrious and popular team members under Graham Arnold - is questionable, given Popovic has opted to call up Portsmouth forward Kusini Yengi, who is just two games back into his return from a three-month lay-off with a knee injury.
There is also no place for Noah Botic, who is arguably the most in-form Australian forward in the A-League Men, and he misses out to Adam Taggart and Brandon Borrello.
Nestory Irankunda has also been snubbed after he was left out of the squad for November's window.
Popovic has, however, given Daniel Arzani a reprieve after blasting the Melbourne Victory winger for his lack of consistency in January.
Since Popovic put him on notice, Arzani has started just one of his seven games for Victory and has failed to score or register an assist.
Australia face Indonesia on March 20 before heading to meet China on Tuesday, March 25 in Hangzhou.
The Socceroos sit second and occupy an automatic qualification berth in their group of six, but four teams including China and Indonesia are just one point behind them.
SOCCEROOS SQUAD
Goalkeepers: Maty Ryan, Paul Izzo, Tom Glover*
Defenders: Aziz Behich, Cameron Burgess, Jason Davidson, Milos Degenek, Jason Geria, Alex Grant*, Fran Karacic, Lewis Miller, Kye Rowles, Kai Trewin*.
Midfielders: Anthony Caceres, Jackson Irvine, Aiden O'Neill, Ryan Teague*, Nectar Triantis*.
Attackers: Daniel Arzani, Brandon Borrello, Martin Boyle, Craig Goodwin, Adam Taggart, Marco Tilio, Nishan Velupillay, Kusini Yengi.
*denotes debutant
