Known for the 1981 hit O Superman and her use of technology in her music, Ms Anderson, Lou Reed's widow, was NASA's first artist in residence.
After appearing at the Brighton Festival in 2011 and 2015 she said she was "so happy" to be appointed as guest director for this year's event.
The festival takes place between 7 and 29 May, and will also feature her work.
Ms Anderson said: "I'm so happy to be serving as guest director of Brighton Festival in its historic 50th year.
"Our theme of home and place is especially relevant with so many people in the world on the move now looking, like all of us, for a place we can belong."
Ms Anderson, who originally trained as a sculptor, is an American experimental performance artist, composer and musician who plays violin and keyboards and sings in a variety of experimental music and art rock styles.
In 1977, she created a tape-bow violin that used recorded magnetic tape on the bow instead of horsehair and a magnetic tape head in the bridge.
The full festival programme will be announced in February, but it has been revealed that Tim Crouch and Spymonkey - both from the city - will re-enact every onstage death from the works of William Shakespeare to mark the 400th anniversary of the Bard's death.
Established in 1967, the first Brighton Festival included appearances by Laurence Olivier, Anthony Hopkins and Yehudi Menuhin.
Previous guest directors include actress Vanessa Redgrave, former Children's Laureate Michael Rosen and Burmese pro-democracy leader Aung San Suu Kyi.
Andrew Comben, chief executive of Brighton Festival, said: "Laurie Anderson has been experimenting, creating and challenging audiences all over the world for almost as long as Brighton Festival has existed - indeed, she's been a part of the festival's journey in past years."
Musician and performance artist Laurie Anderson has been announced as guest director of the Brighton Festival.