Promoted Sampdoria consigned AC Milan to a shock 1-0 defeat at San Siro on Sunday, Andrea Costa scoring the winner in the second half to give Milan the worst possible start after a traumatic close season.
Milan, Serie A runners-up last term, had the spine ripped out of their squad over the summer, with superstars Thiago Silva and Zlatan Ibrahimovic sold to Paris Saint-Germain and a glut of long-serving players moving on.
Sampdoria, who start the new campaign with a one-point deduction over the 'Calcioscommesse' betting scandal, were able to celebrate their first goal at San Siro since the 2007-08 season.
It came in the 59th minute, when left-back Costa rose high above the home defence to head in a corner from the right.
That stirred the hosts into action, with Mario Yepes and Kevin-Prince Boateng hitting the woodwork.
But Ciro Ferrara's men held on to take the points, although there was an injury-time scare when Sampdoria's Argentine goalkeeper Sergio Romero had to be at his best to repel Boateng's header.
Sampdoria were the worthy winners though, and could have even taken a first-half lead via lone Brazilian striker Eder.
Rivals get it right
Later, Inter Milan showed their city rivals how it should be done with a 3-0 win at another promoted side, Pescara.
Dutch international Wesley Sneijder opened the scoring against the run of play in the 17th minute after a free-flowing move, sweeping the ball home from the edge of the box.
Two minutes later, Sneijder found new signing Antonio Cassano, formerly of Milan, who slid the ball over to Diego Milito to convert from close range.
The hosts had an eye-catching opportunity to reduce the deficit just before the break but Emmanuel Cascione's header was kept out by the lightning reflexes of Inter goalkeeper Luca Castellazzi.
Milito then set up Inter's third nine minutes from time when he slid the ball into the box from the right for Philippe Coutinho to slot home.
Inter sit top of the fledgling table alongside Napoli, who came away from their trip to Palermo with a 3-0 win, courtesy of goals from Marek Hamsik, Christian Maggio and Edinson Cavani.
Elsewhere, Chievo beat Bologna 2-0 and Genoa saw off visitors Cagliari by the same scoreline.
An injury-time strike by Uruguayan forward Nicolas Lopez earned Roma a 2-2 draw with Catania, while Lazio beat Atalanta 1-0 and the game between Siena and Torino ended in a goalless stalemate.
On Saturday, Juventus overcame a sluggish first-half display to kick off the defence of their Serie A crown with a 2-0 victory at home to Parma.
A pair of quick-fire goals shortly before the hour from Stephan Lichtsteiner and Andrea Pirlo proved the difference between the sides, after Arturo Vidal had seen a first-half penalty saved.
Juve have not lost in the league since May 15, 2011 and their unbeaten run now stands at 24 victories and 16 draws, which is a record in the Italian top flight.
In the first match of the season, Fiorentina came from behind to beat Udinese 2-1 thanks to a brace from Montengrin attacker Stevan Jovetic, who claimed his decisive second goal in injury time