Halka ay Milan xilli ciyaareedkii xigay ku badisay horyaalka. Milan waxay marti gelisay Genoa 25kii Sebtember 2010, iyadoo Pirlo uu bixiyay kubbad kor loo qaaday oo ka sarreysa difaaca si uu u sii daayo weeraryahanka Zlatan Ibrahimović si uu u dhaliyo goolka keli ah ee ciyaarta. Bishii Oktoobar 2, Pirlo wuxuu dhaliyay gool 40-yard ah oo ka dhan ah Parma si uu Milan u siiyo guushii ugu horreysay ee ay ku guuleystaan xilli ciyaareedkii 2010-11. 14kii Maajo 2011, Pirlo wuxuu ka soo muuqday kulankiisii ugu dambeeyay ee Milan, isagoo ku soo biiray badhkeedkii si uu ugu beddelo Ambrosini markii ay kooxdu u dabaaldegtay horyaalkooda Serie A
4-1 oo ay kaga badisay Cagliari. Afar maalmood ka dib, Pirlo wuxuu xaqiijiyay inuu ka tagi doono Milan dhamaadka xilli ciyaareedka 2010-11, kadib go'aan wadajir ah oo ah inuusan cusbooneysiin qandaraaskiisa. Xilli ciyaareedkiisii ugu dambeeyay ee Milan, Pirlo wuxuu ka soo muuqday horyaalka kaliya 17 jeer macalinka Massimiliano Allegri, isagoo dhaliyay kaliya hal gool iyo seddex caawin, isagoo ku guuleystay horyaalkiisii labaad ee Serie A ee Milan xilli ciyaareedkaas, sidoo kale wuxuu gaadhay wareega 16-ka ee UEFA Champions League, iyo semi-finalka Coppa Italia.