Milito, 31, scored the winning goals in the three key matches as Inter claimed last term's unprecedented Italian treble of Serie A, Champions League and Italian Cup in his first season at the club. He netted 22 league goals last season.
"It's an immense honour. For me 2010 will always be a truly unforgettable year," late bloomer Milito said at the ceremony dubbed the "Italian football Oscars."
The Argentine beat off competition from Dutch team-mate Wesley Sneijder, who has missed out for a second time after being left off the three-man shortlist for the FIFA Ballon d'Or won by Lionel Messi this month.
Mourinho was odds-on to win the best coach award for a second straight year despite quitting Inter for Real Madrid immediately after sealing May's treble.
"I'm sorry for not being there but (Wednesday's) cup semi-final with Sevilla stopped me from coming," Mourinho said.
"To receive the Oscar is great because for me to have respect is important... also from my opponents. Serie A is tough and I see that now I am away."
Inter's Walter Samuel, out for the season with injury, shared the best defender gong for 2009/10 with Juventus centre-back Giorgio Chiellini and Udinese's Antonio Di Natale was voted best Italian player for topping last term's scoring charts.
Palermo's Argentina playmaker Javier Pastore won best young player.
