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- Leslie Bibb as Kate Bohr, a country club wife from Austin, Texas, one of three longtime friends reuniting on a girls' trip
- Carrie Coon as Laurie Duffy, a corporate lawyer and recent divorcée from New York, one of three longtime friends reuniting on a girls' trip
- Walton Goggins as Rick Hatchett, a rugged and mysterious man with a chip on his shoulder, traveling with his young girlfriend Chelsea
- Sarah Catherine Hook as Piper Ratliff, a college senior studying religion and middle child of Timothy and Victoria
- Jason Isaacs as Timothy Ratliff, a financier in jeopardy from Durham, North Carolina, vacationing with his wife, Victoria, and kids Saxon, Piper, and Lochlan
- Lalisa Manobal as Thidapon "Mook" Sornsin, a health mentor for guests of the White Lotus
- Michelle Monaghan as Jaclyn Lemon, a successful television actress based in Hollywood, one of three longtime friends reuniting on a girls' trip
- Sam Nivola as Lochlan Ratliff, a shy high school senior and Timothy and Victoria's youngest child
- Lek Patravadi as Sritala Hollinger, one of the owners of the White Lotus, who pioneered its health program
- Parker Posey as Victoria Ratliff, Timothy's wife and mother to Saxon, Piper, and Lochlan
- Natasha Rothwell as Belinda Lindsey, a spa manager from the White Lotus in Hawaii, attending a work exchange. Rothwell reprises her role from the first season.
- Patrick Schwarzenegger as Saxon Ratliff, Timothy and Victoria's oldest child, who works for his father's company
- Tayme Thapthimthong as Gaitok, a security guard at the White Lotus
- Aimee Lou Wood as Chelsea, a bubbly free spirit from Manchester traveling with Rick, her much older boyfriend
- Jon Gries as "Gary" / Greg Hunt, a man involved with Chloe and the widower of Tanya McQuoid. Gries reprises his role from the first and second seasons.
