The 51-year-old has signed a two-year deal with the club just 24 hours after Andrea Stramaccioni was relieved of his duties
Former Sampdoria trainer Mazzarri had been heavily linked with a move to San Siro after guiding the Partenopei to an impressive second-place finish in Serie A this season.
The 51-year-old succeeds Andrea Stramaccioni, who was sacked on Friday.
"FC Internazionale would like to announce that the club has appointed Walter Mazzarri as the new head coach," read a statement on the club's official club website.
"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 move brings to an end Mazzarri's four-year reign in Campania following the club’s highest league finish in over 20 years, sealing qualification for next season's Champions League in the process.
However, Mazzarri will not be involved in any European competition next year as Inter did not qualify for either the Champions League or Europa League after a disappointing campaign saw them end the season in ninth.