Former Portsmouth pair Kevin-Prince Boateng and Sulley Muntari did the damage in Italy as Massimiliano Allegri's side defended stoutly causing the Catalan giants plenty of trouble on the break.
The opening goal came in controversial circumstances in the 57th minute when Riccardo Montolivo's free-kick deflected onto the hand of Cristian Zapata with Boateng receiving the crumbs to rifle home. The Barcelona players were furious that referee Craig Thomson did not call for handball but he instead awarded the goal to the home side.
Milan were able to quell the creativity of Lionel Messi, Andres Iniesta and Cesc Fabregas and it paid dividends when they conjured a second goal with nine minutes remaining. Muntari got on the end of Stephan El Shaarawy's lobbed ball to volley home from 10 yards which sent shockwaves through the Barca camp.
The Rossoneri fans reacted as they would be expected to - with pure jubilation - and they will now be looking forward to the return bout at the Nou Camp on March 12.
2012/13 UEFA Champions League - Round of 16 first leg
San Siro, Milan - 75,000