The 38-year-old striker is in his second spell at the club after he joined them in January on a free transfer after his contract with LA Galaxy ended.
"I'm like Benjamin Button, except I've always been young, never old", he added, referring to the main character in a 2008 Oscar-winning Hollywood movie about a man who ages in reverse.
Ibrahimovic scored 57 goals for Inter when he spent three years at the club between 2006-2009 before he made the switch to Barcelona.
"They tell me I'm old and exhausted but I'm just getting warmer", Ibrahimovic joked after Wednesday's game, which pulled Milan within a point of fifth-place Roma. His second goal came in the 58th minute.
Despite securing a runners-up finish in his first season with Inter, head coach Antonio Conte took aim at the Nerazzurri afterwards, claiming neither he nor his players received protection from the club amid criticism.
However, Milan went straight down the other end and deservedly doubled their lead, with Calhanoglu reaching Ibrahimovic's knockdown to thrash home. However, Sampdoria managed to restore some pride when Kristoffer Askildsen scored one in the 87th minute. Giacomo Bonaventura then assisted Milan's Rafael Leao for the final score in stoppage time.
He was awarded with a momento by club legend Paolo Maldini and in the video uploaded on Milan Twitter handle, Ibrahimovic had said: "Thank you all for your congratulatory messages for my 100th appearance in Rossoneri colours".