Paraguay, bottom of their qualifying group and with almost no hope of reaching a fifth World Cup finals in a row, managed a shock 3-3 draw away to an unusually sloppy Germany side on coach Victor Genes's debut.
A largely experimental Spain team earned a 2-0 away win over Ecuador to keep the European flag flying in the steamy Pacific port city of Guayaquil with goals from Alvaro Negredo and Santi Cazorla for the world champions.
England, by no means sure of a direct berth into the World Cup finals, fought back twice for a 3-2 win over Scotland at Wembley in an enthralling first clash between the bitter rivals since 1999.
In the night's only World Cup qualifier, Russia blew a chance to overtake Portugal at the top of European Group F when they were upset 1-0 by Northern Ireland in Belfast, Martin Paterson scoring the only goal two minutes before halftime.
The 2014 World Cup hosts Brazil, fresh from their Confederations Cup triumph, were disappointing in Berne where they failed to recover from a Dani Alves own goal just after the interval.
Brazil coach Luiz Felipe Scolari argued that his team were less prepared than the Swiss for an international date at the end of the mid-year off-season.
Argentina, missing captain Messi due to muscle fatigue, won their first meeting with Italy for 12 years with striker Gonzalo Higuain, a fine successor to Gabriel Batistuta, opening their account with his 21st goal in 34 internationals.
Substitute midfielder Ever Banega added the second before Lorenzo Insigne pulled one back in the match in Rome in honour of Argentine-born Pope Francis and preceded on Monday by the visit of both teams to the Vatican.
"When Leo's there we have extra potential up front but we were able to play and win without him," midfielder Angel Di Maria told reporters referring to Messi.
Germany were 15 minutes away from a shock defeat, having ended the first half 3-2 down to Paraguay, but substitute Lars Bender came to their rescue with a 75th-minute equaliser.
A leveller from Cristiano Ronaldo, Messi's regular rival for FIFA's World Player of the Year award, salvaged a 1-1 draw for Portugal at home to the Netherlands in the Algarve while Belgium and France were deadlocked in a 0-0 draw in Brussels.
Another of the world's leading strikers, Zlatan Ibrahimovic, got a hat-trick as Sweden beat neighbours Norway 4-2 in Stockholm.
He was, though, pipped for goal of the night by veteran Anders Svensson who hammered home a twisting, dipping shot for their fourth in his 142nd international.
U.S. forward Jozy Altidore also scored three goals as Juergen Klinsmann's side came back from two goals down to beat Bosnia-Herzegovina 4-3 in Sarajevo.
England striker Rickie Lambert only scored once but it was a dream international debut for the substitute at the age of 31 as he scored the winner against Scotland with his first touch by heading home a corner seconds after coming on.
"I've been dreaming of that all my life, it mans so much," said an elated Lambert.
Montenegro, who lead European Group H by two points ahead of England having played a game more, were held 1-1 by Belarus in Zhodino.
Colombia beat Serbia 1-0 in Barcelona with a late goal from midfielder Fredy Guarin while Uruguay and Chile, direct rivals for places at the 2014 finals, enjoyed high-scoring victories.
Diego Forlan netted two first half goals as Uruguay won 4-2 in Japan with unsettled Liverpool striker Luis Suarez also on the scoresheet as both players increased their joint record national team tally to 36 each.
Chile crushed hapless Iraq 6-0 in Denmark with Alexis Sanchez in fine form, scoring twice and laying on two goals for winger Jean Beausejour.
Jordan, preparing to face Uzbekistan in the Asian playoff for a berth in the intercontinental decider against South America's fifth-placed team, beat Libya 2-1 in Amman.