The Argentine hit twice as the away team were put to the sword in the Stadio Olimpico, Osvaldo and Burdisso also hitting home in a comfortable victory
The Giallorossi's Argentine contingent were the architects of the visitors' downfall, as goals from Nicolas Burdisso and Pablo Osvaldo were added to by an impressive double by Erik Lamela.
Late strikes from Giampaolo Pazzini and Bojan Krkic gave the scoreline a more flattering appearance, but could not hide what was an extremely disappointing 90 minutes for Massimiliano Allegri's charges.
Saturday's clash at the Stadio Olimpico began at a frenetic pace; Milan were threatening after a matter of seconds through Stephan El Shaarawy, the Serie A top scorer advancing on goal and firing just wide from the edge of the area.
Roma forced Marco Amelia into action through Daniele De Rossi's decent effort from distance, and the keeper did fantastically to make an acrobatic save from Pablo Osvaldo, tipping the Argentine-Italian's effort over the crossbar. Osvaldo took the corner kick himself, and his cross found Burdisso who headed perfectly to open the scoring early on in favour of the home team.
Milan searched for an instant reply, and should have levelled when El Shaarawy broke through; the youngster denied his 15th goal of the season by an excellent save from Mauro Goicoechea. The Rossoneri would pay dearly for that miss, as Roma doubled their advantage just moments later.
Federico Balzaretti and Francesco Totti combined well on the left, leaving the veteran club icon to put in the cross. His centre was perfectly placed for Osvaldo, who got the better of Mario Yepes to leave the Colombian flailing and head past Amelia. Massimiliano Allegri's men were shell-shocked at having fallen two goals behind in the opening exchanges of the match, but it was only to get worse.
The visitors were slack with possession following a Giallorossi cross, and Daniele De Rossi was left with time on the edge of the area. Lamela was unmarked and picked out with a delightful reverse pass, and youngster became the third Argentine on the Roma scoresheet as he converted with ease past the hapless Milan keeper.
Having played such a key part in Roma's outstanding first-half performance, Totti was handed a clear opportunity to put the game definitively out of Milan's reach just four minutes after the interval. The playmaker was played clean through against Amelia, but amazingly scuffed his effort and sent the ball agonisingly past the post.
Milan had been shambolic all evening from crosses, and it was once more aerially that they conceded the fourth. Lamela won the ball with ease six yards out after being located by Balzaretti's centre, and Amelia's despairing dive was in vain as the ex-River Plate wonderkid marked his 10th goal of the season.
From that point onward the Rossoneri had little more than pride to play for, but still could not find a way past Goicoechea; the Uruguayan promise coming up big to deny both Robinho and Boateng in a great double stop. He would then top that effort with three great saves in quick succession, proving that it just was not going to be Milan's day in the Italian capital.
The Roma victory was marred slightly by a bizarre incident involving Marquinhos towards the end. The Brazilian defender was given a straight red card for an innocuous use of the arm 30 metres from his own goal that merited no more than a booking. Goicoechea then handed Milan the chance for a consolation, conceding a penalty in the dying minutes converted by substitute Pazzini. The goal sparked a revival for the visitors, who added a second through Bojan who converted against his former club.
It was all too late, however, and the 10-man hosts held firm to record a memorable victory against their rivals.