In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples’ needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples’ communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples’ counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.