It's 1994 in the city of Kigali, Rwanda. Hutu extremists are slaughtering their Tutsi neighbors by the thousands along with any Hutu moderates who may get in their way. Despite his wife, Tatiana (SOPHIE OKONEDO) and her family being Tutsis, Paul Rusesabagina (DON CHEADLE) -- the house manager of the luxurious Belgian owned Mille Collines Hotel -- is still trying to do his job.
With his aide, Dube (DESMOND DUBE), by his side, he goes to visit black marketer and fervent Hutu supporter George Rutagunda (HAKEEM KAE-KAZIM) for hotel supplies. A smooth business operator who'd rather stay out of political issues, Paul's been storing up favors with the likes of Colonel Oliver (NICK NOLTE) of the United Nations and General Bizimungu (FANA MOKOENA), the latter of whom is willing to help Paul in exchange for bribes of fine spirits.
Returning home one night, Paul discovers his family and neighbors hiding in his house. It seems that Tutsi rebels have killed the country's president and Hutu soldiers are now executing every Tutsi they can find. Faced with a precarious situation, Paul manages to convince the angry men to allow them safe passage back to his hotel. With the management now gone, Paul is in charge and gets the support of the international owner (JEAN RENO) to try to convince some of the less than loyal workers, such as Gregoire (TONY KGOROGE), to keep working.
With TV cameramen Jack (JOAQUIN PHOENIX) and reporter David (DAVID O'HARA) capturing the chaos and growing genocide, and Red Cross worker Pat Archer (CARA SEYMOUR) delivering more and more orphans to the hotel, Paul has his hands full, especially when Col. Oliver informs him that the U.N. won't be sending any additional forces to help them. As things progressively worsen and he tries to get word of his in-laws' fate, Paul does what he can to keep the Hutu killers at bay, all while taking in a growing number of refugees that soon tax his physical and mental resources.