After months of talks, the Italian and Argentinian federations managed to set up Wednesday's encounter in Rome that will be dedicated to the pope — a football fan who comes from Argentina and is the son of Italian immigrants.
Italy's last match with Argentina was also a friendly in Rome, in 2001, which Argentina won 2-1. Before that, Diego Maradona's Argentina knocked host Italy out of the 1990 World Cup on penalties in a memorable semifinal in Naples.
Among other high-profile matches to be played on Wednesday, England faces Scotland, world and European champion Spain travels to Ecuador, Belgium hosts France, Switzerland hosts Brazil and Luis Suarez's Uruguay travels to Japan without the injured Edinson Cavani.
Italy and Argentina players are set to meet the pope in an audience at the Vatican ahead of the match, but he is not expected to be in the stands at Stadio Olimpico.
Italian coach Cesare Prandelli first came up with the idea of organizing the match.
"It was just a sudden flash, after watching Pope Francis and his first appearances in public," he recently told sports daily La Gazzetta dello Sport. "He generated a tremendous sense of fondness and approval. The thought of 'his countries', Italy and Argentina, immediately entered my head. Two squads leaving together, from the same hotel, to have an audience full of joy and happiness with the pope."
It will be Italy's first match since the Azzurri finished third at the Confederations Cup. AC Milan striker Mario Balotelli has been included in the squad despite a slight calf injury, as well as fellow striker Pablo Osvaldo, who has been recalled after falling out with coach Prandelli.
The Roma striker, who was born in Buenos Aires and will likely get a chance to face his native country, was kicked out of the Confederations Cup squad for insulting his club coach at Roma — a breach of Prandelli's strict code of ethics.
Argentina and Barcelona star Lionel Messi could miss the match after sitting out his club's final preseason friendly in Malaysia with a muscle strain in his left leg.
Messi's new Barcelona teammate, Brazilian striker Neymar, is expected to play a part against Switzerland after his inclusion in the squad by coach Luiz Felipe Scolari.
The Brazilian coach is relying on many the same players he used at the Confederations Cup, with 19 of the 20 in the squad for the team's friendly in Basel drawn from the group in Brazil.
England and Scotland are meeting for the first time in nearly 14 years when they play at Wembley amid speculation over Wayne Rooney's future. The Manchester United striker, who reportedly wants to leave the Red Devils for Chelsea, missed United's Community Shield win over Wigan with a shoulder injury but took part in training with England on Monday.
"There was no doubt in my mind in the session that he was not suffering from a physical injury," England manager Roy Hodgson said. "Myself, my coaches and our fitness people will analyse everything and — in tandem with Wayne — will give him the right amount of minutes."
Seeking a move away from Liverpool, Suarez will find some comfort with the Uruguay team after facing harsh criticism on Merseyside for publicly voicing his desire to leave Anfield.
Another player with his future reportedly hanging in the balance, Tottenham winger Gareth Bale, won't play for Wales against Ireland in Cardiff because of a foot injury. The 24-year-old Bale has been selected for the friendly match but trained on his own Monday as the Welsh federation said it would not take any risk with his injury.
Bale is coveted by Real Madrid and has not played for nearly a month with his north London club.