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, celebrated 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.
Sunday's late games include Inter Milan at Pescara and Roma hosting Catania.
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.