Cholera, which is caused by Vibrio cholerae, persists as a devastating acute diarrheal disease. Despite availability of information on socio-cultural, agent and hosts risk factors, the disease continues to claim lives of people in Tanzania. The present study explores spatial patterns of cholera cases during a 2015–16 outbreak in Mwanza, Tanzania using a geographical information system (GIS) to identify concentrations of cholera cases. This cross-sectional study was conducted in Ilemela and Nyamagana Districts, Mwanza City. The two-phase data collection included: 1) retrospectively reviewing and capturing 852 suspected cholera cases from clinical files during the outbreak between August, 2015, and April, 2016, and 2) mapping of residence of suspected and confirmed cholera cases using global positioning systems (GPS). A majority of cholera patients were from Ilemela District (546, 64.1%), were males (506, 59.4%) and their median age was 27 (19–36) years. Of the 452 (55.1%) laboratory tests, 352 (77.9%) were confirmed to have Vibrio cholerae infection. Seven patients (0.80%) died. Cholera cases clustered in certain areas of Mwanza City. Sangabuye, Bugogwa and Igoma Wards had the largest number of confirmed cholera cases, while Luchelele Ward had no reported cholera cases. Concentrations may reflect health-seeking behavior as much as disease distribution. Topographical terrain, untreated water, physical and built environment, and health-seeking behaviors play a role in cholera epidemic in Mwanza City. The spatial analysis suggests patterns of health-seeking behavior more than patterns of disease. Maps similar to those generated in this study would be an important future resource for identifying an impending cholera outbreak in real-time to coordinate community members, community leaders and health personnel for guiding targeted education, outreach, and interventions.