In the fictional Republic of Zubrowka during the 1930s, the once-luxurious Grand Budapest Hotel is on the decline. The story begins as Zero Moustafa, the hotel's owner, recounts its glory days to a young writer. Zero, then a lobby boy, becomes the protégé of the hotel's concierge, Gustave H., a man known for his dedication to the establishment and its guests, particularly the wealthy, elderly women. Gustave prides himself on providing first-class service, resulting in a fanatically loyal clientele.

Tragedy strikes when one of Gustave's favorite patrons, Madame D., is found dead under mysterious circumstances. She bequeaths a valuable Renaissance painting to Gustave, much to the chagrin of her scheming family, who had expected to inherit her fortune. Wrongfully accused of her murder, Gustave is thrust into a quest to clear his name and secure his legacy. Together with loyal Zero and Zero's love interest, the pastry chef Agatha, they embark on an adventurous pursuit intertwined with theft, a prison break, and a battle over the family fortune, all set against the backdrop of a looming war that threatens to engulf Zubrowka and change their lives forever.