The game at the Letzigrund in Zurich was played against the backdrop of a match-fixing scandal back home that prompted Italy coach Cesare Prandelli to say he would not mind his side pulling out of the European Championship if it was the right move.
Friday's performance was a defensive nightmare for Italy, who conceded only twice in 10 games during qualifying, with Russia's second and third goals coming from defensive mix-ups involving substitute goalkeeper Morgan De Sanctis.
Italy had created more chances in the opening hour but their rearguard always looked shaky and they fell to pieces when Russia, who could have scored three times ahead of the break, went ahead through Alexander Kerzhakov just before the hour.
Roman Shirokov then added two late goals.
It was Italy's third successive match without scoring following 1-0 defeats by Uruguay in November and the United States in February and their heaviest loss since Prandelli took charge following the 2010 World Cup.
Italy have been drawn in a tough Group C at Euro 2012 with world and European champions Spain, Croatia [ Images ] and Ireland.
Mario Balotelli [ Images ] drew a blank for the Italians, disappearing from the action in the last half hour after a bright opening.
"I have to do tests, we didn't have time for lots of preparations, there is not much time," said Prandelli.
"The first half was open, both teams could have scored and the first 10 minutes of the second half were also very good but when the goal came we lost all our energy. I'm not sure if it was physical or psychological."
"This is something I have to find out, to help rebuild the confidence. Perhaps it's good to suffer a bad game now as it means we have our feet back firmly on the ground and know how much we have to work.
"We have to regain our strength and fight for every ball, as in the qualification," he added.
Italy's match-fixing scandal led Prandelli to drop left back Domenico Criscito from his squad after police said the player was formally under investigation.
Criscito has denied any wrongdoing.
Jeered off the pitch by the mainly Italian crowd, Italy's nightmare began just after Antonio Cassano failed to turn Balotelli's cross into the net.
Russia broke down the other end and Kerzhakov, allowed too much space, fired the opening goal past De Sanctis, who had replaced Gianluigi Buffon at halftime, from Shirokov's pass just before the hour mark.
The second goal 15 minutes from time came after De Sanctis and Christian Maggio went for the same ball and the hapless keeper cleared to Shirokov who slid it into an empty net.
The Zenit St Petersburg [ Images ] player benefitted from more sloppy defending in the 89th minute to round off the victory.
Italy began the match with Balotelli and Cassano in attack, Daniele De Rossi and Claudio Marchisio in the heart of midfield, Riccardo Montolivo between them and the forwards, with Andrea Pirlo as a deep-lying playmaker.
Pirlo was involved in nearly all of Italy's best attacks, his floated passes over the Russian backline and angled passes between their defenders spelling danger almost every time.
In the fourth minute, he picked out Balotelli, who controlled the ball on his chest and produced a powerful half-volley which was tipped over by Vyacheslav Malafeyev.
A similar chipped pass was just too long for the marauding Balotelli, who also just failed to make contact with De Rossi's low cross after Pirlo again opened up the Russian defence.
Balotelli tried too often to go it alone and ended up losing possession.
However, Italy's main problems were at the back, usually their strong point. They looked exposed at the back and often lost possession as they tried to play their way out of defence.
Russia weaved some neat passing patterns and could easily have scored two or three goals before halftime, but repeatedly wasted their chances.
Kerzhakov hit the foot of the post, Konstantin Zyryanov twice shot wide from good positions and Shirokov had a shot parried by Buffon.
Italy's only other warm-up match before they face Spain in their opening match on June 10, against Luxemburg in Parma on Tuesday, was cancelled following the earthquake which hit the north of the country.