In the first part of Open City, Julius, the protagonist, is shown getting used to his new environment. He has moved to the United States to pursue his training and career in psychiatry, and he sets out to explore Manhattan. Walking through the city streets, he becomes familiar with the moods and tones of the different neighborhoods. He also thinks about the city’s colonial history as New Amsterdam, which he learned from a book that his patient wrote. While his efforts are partially successful, he still does not feel completely at home. He also thinks about his recently ended relationship with Nadege, who had been his girlfriend in New York. She decided to move to California. He is also concerned with the declining health of his former professor and mentor, Dr. Saito.
The setting of the second part switches to Europe, where he spends a month. Julius goes to Brussels looking for his German grandmother, who is his mother’s mother. He wants to re-connect with her because he had rarely seen her. He grew up in Nigeria—where his father was from—and she and his mother were almost totally estranged from him. Now she is his only remaining grandparent, and both his parents are also dead. Julius’s alienation is further marked when he has a casual sexual encounter; he lies and tells this partner his name is Jeff. He also dines with a Dr. Maillotte, a woman with strong opinions about Africans and immigrants who he met on the airplane. He learns from his apartment’s landlord about the racial and anti-immigrant tensions in the city. Julius befriends a Moroccan bartender named Farouq, and he encounters several Rwandans, all of which lead him into further consideration of his Nigerian heritage and the reasons that influenced his decision to move to the United States for college.