The left-back joins a Milan team that failed to qualify for European competitions last season after experiencing their worst Serie A finish in a decade.
The club reinstated former manager Massimiliano Allegri for a second term in May and added former Real Madrid midfielder Luka Modric earlier this month.
Estupinan, 27, made 104 appearances for Brighton after transferring to the Premier League side from Villarreal in 2022.
"I have enjoyed collaborating with Pervis, and he has made a notable impact on the club during his time here," stated Brighton manager Fabian Hurzeler.
"He is at a point in his career where he seeks a new challenge, and this chance to play in Serie A provides that. I want to thank Pervis for his contributions to the club and wish him all the best moving forward."
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