The 43-year-old Italian has come in to replace Graham Potter, who left to join Chelsea earlier this month.
De Zerbi was previously in charge of Shakhtar Donetsk but left this summer following Russia's invasion of Ukraine.
De Zerbi has signed a four-year contract at the AMEX Stadium and will begin his reign with a trip to Liverpool on October 1 after the international break.
Brighton have made a bright start to the season, sitting fourth on the table with a game in hand.
Albion chairman Tony Bloom told the club's official website: "I am absolutely thrilled Roberto has agreed to become our new head coach.
"Roberto's teams play an exciting and courageous brand of football, and I am confident his style and tactical approach will suit our existing squad superbly."
Brighton chief executive Paul Barber added: "We looked at a range of excellent candidates but Roberto was our number one choice from the start and the only person we spoke to.
"It's no secret our chairman is constantly monitoring potential coaches, both here in our domestic leagues, throughout Europe and across the world as part of our succession planning work.
"We feel Roberto is the ideal cultural and technical fit for Brighton and Hove Albion, and the right person to continue the club's progress and work with this outstanding group of players."
