Female homicide is a global phenomenon with a higher prevalence in countries in Asia, Africa, and the Americas. Life expectancy in Brazil is compromised by the high risk of death from male and female homicides, a growing social problem. This study aimed to integrate different public datasets and describe the sociodemographic, criminal, and medicolegal characteristics of the homicides of girls and women occurring in Porto Alegre, southern Brazil, from 2010 to 2016. The data were obtained from autopsy reports, police reports, and records from crime scenes. During this period, there was a significant increase in overall standardized rates of female homicides (4.98 to 10.85), with a pronounced increase in non-gender-related deaths, especially due to urban violence, such as involvement in drug trafficking and other crimes and robbery resulting in death. Young (15–29 years of age), non-White women were the most affected. Increased female homicide rates due to non-gender-related factors is a new and worrying phenomenon in Brazil. Obtaining specific data on the profile of victims and characteristics of violence is a crucial step in facing the problem and directing public policies.