The Brief Wondrous Life of Oscar Wao begins with the titular character Oscar de León, a young Dominican boy from New Jersey who worries that he will never lose his virginity. Unfortunately, his shyness and love of science fiction make him unsuccessful with women. As a college student, Oscar falls into depression and attempts suicide while drunk by jumping off of a bridge. His family, worried about his well-being, send his sister's boyfriend Yunior to live with him while he recovers. Despite frequent fights with his family and a second suicide attempt, Oscar is able to graduate with his degree.
Following his college graduation, Oscar works as a substitute teacher by day and a science fiction writer by night. Although he dreams of writing an epic science fiction work, he is lonely and romantically unfulfilled. He moves to the Dominican Republic to change his circumstances and falls in love with a prostitute named Ybon. Ybon is kind to him but doesn't return his affections. Oscar's infatuation throws Ybon's boyfriend, a police capitán, into a jealous rage, and he beats Oscar into a coma after kidnapping him.
While recovering from his injuries, Oscar returns to New Jersey but cannot stop thinking about Ybon. When he's well enough to travel, he borrows money from Yunior and travels back to the Dominican Republic to win Ybon's heart. Although hesitant at first to associate with him, Ybon's care for Oscar deepens and they have sex. Word returns to Ybon's boyfriend however, and enraged, he drags Oscar to the sugarcane fields and beats him to death.