Cristiano Ronaldo looked to have earned Portugal a draw in Geneva with a 21st-minute equaliser but the Real Madrid forward was upstaged by his Barcelona rival, who converted from the spot with seconds remaining.
Karim Benzema was France's matchwinner in Paris, the Real Madrid striker scoring in the 54th minute after good build-up play by Jeremy Menez. Brazil was down to 10 men by that stage following the sending-off of Hernanes.
In other high-profile international friendlies, Manchester City winger David Silva scored an 86th-minute winner in Spain's 1-0 victory over Colombia to end the team's poor recent run of results, Italy drew 1-1 in Germany and England beat Denmark 2-1.
Messi and Ronaldo - who both play their club football in Spain and are arguably the world's leading two players - were always going to hog the limelight in the first match between Argentina and Portugal since 1972.
Messi had the last laugh, tucking away his penalty for his 16th international goal after Javier Pastore was adjudged to have been fouled.
"We always enjoy seeing two great players on the same field," Argentina coach Sergio Batista said. "I liked both of them tonight. Lionel was at a higher level."
Argentina went ahead in the 14th when Madrid winger Angel di Maria ran on to a pass by Messi to lift a finish over advancing goalkeeper Eduardo, but Ronaldo levelled by sliding home seven minutes later after Hugo Almeida had flicked the ball on.
The France-Brazil match at the Stade de France was a repeat of the 1998 World Cup final, which the French won 3-0, and the hosts deservedly got the better of their South American opponents again 11 years on.
France, who claimed a fifth straight win and built on the 2-1 away victory over England in November, made the most of the numerical advantage given to the team by Hernanes' red card, brandished to the midfielder for a dangerous tackle on Benzema.
The striker got back to his feet to lead the French charge, squandering a host of chances except for the one that brought France victory.
Menez went past two players and crossed the ball for Benzema to tap in for his 12th goal in 33 internationals.
Benzema also brought two great saves out of Brazil goalkeeper Julio Cesar, while the visitors' best chance for an equaliser came when substitute Hulk saw a shot pushed away by home goalkeeper Hugo Lloris.
"The wins against England and Brazil should give us a lot more confidence individually and collectively," Blanc said. "I hope we can use it in the future for the important (2012 European Championship) qualifiers coming up."
Spain was winless in its last three friendly games going into the international against Colombia, its most recent match being a 4-0 thrashing by Iberian neighbour Portugal.
The world and European champions struggled to keep up with the visitors at times at Madrid's Santiago Bernabeu Stadium but snatched a morale-boosting victory when Silva turned in a cross right winger Jesus Navas.
Germany and Italy were playing in Dortmund, the venue of their last meeting when the Italians won 2-0 after extra time in the semifinal of the 2006 World Cup.
The Germans were heading toward avenging that loss when Miroslav Klose scored in the 17th minute, latching on to a cross by Bayern Munich midfielder Thomas Mueller.
Giuseppe Rossi grabbed a draw for Italy in the 81st, however, when the Villarreal striker got away from Per Mertesacker and beat goalkeeper Manuel Neuer at the second attempt.
Ashley Young came off the bench to grab England's 68th-minute winner in Copenhagen, becoming the second Aston Villa forward to score after Darren Bent had cancelled out the opener netted by Denmark defender Daniel Agger in the eighth.
Wesley Sneijder, Klaas-Jan Huntelaar and Dirk Kuyt were the goalscorers for the Netherlands in a 3-1 victory over Austria, while in the night's most surprising result Luxembourg - ranked 131st in the world rankings - upset 20th-ranked Slovakia 2-1.
