The 2010 Champions League winners have suffered a series of blows and gone through five coaches since their unprecedented treble under Jose Mourinho.
"FC Internazionale would like to thank Andrea Stramaccioni for the great commitment and professionalism he showed in a particularly difficult year. Walter Mazzarri has signed a two-year deal, " the club said on their website.
"We needed to make this change because this year will be difficult and I thought that there was a need for a manager with the experience of Mazzarri," Inter president Massimo Moratti told reporters on Friday.
"That doesn't change the fact that I have a high regard for the talent and potential of Stramaccioni and I'm convinced he will become one of the best Italian managers.
"He's been very unlucky recently and maybe right now he needs to go somewhere easier than Inter, and with the year he's had he will find somewhere."
The 37-year-old Stramaccioni surprisingly stepped up from managing Inter's youth setup to take charge of the first team last March following the sacking of Claudio Ranieri.
Early this season Inter looked to be title challengers and a run of seven straight wins finished with them ending Juventus' 49-match unbeaten streak and moving a point behind the league leaders.
