The death of a woman while pregnant or within 42 days of delivery, regardless of the cause of death, or even up to one year after the end of the pregnancy, due to causes related to or aggravated by pregnancy remains a critical public health problem globally and in Colombia. While the country shows a general decreasing trend (preliminary Maternal Mortality Ratio 38.6/100,000 live births in 2023), significant regional disparities persist. Understanding precise underlying causes, especially in high-complexity referral centers, is vital. This study describes the sociodemographic and anatomopathological characteristics associated with autopsy-verified maternal mortality cases at a Level-4 hospital in southwestern Colombia (2000-2023). A descriptive observational retrospective study analyzed 42 maternal mortality cases verified by clinical autopsy (2000-2023) at the Pathology Department of Universidad del Valle, a Level-4 referral center in Cali, Colombia. Cases met the WHO definition. Data on sociodemographic, clinical, and pathological characteristics were retrospectively extracted from clinical records and autopsy reports. The analysis of 42 autopsies (2000-2023) showed that 85.7% were early maternal deaths. Indirect causes predominated (57.1%, n = 24) over direct (42.9%, n = 18). Septic shock was the main indirect cause (65.2% of indirect), often from endemic infections. Hypovolemic shock due to PPH was the main direct cause (50% of direct). A high proportion were from subsidized/uninsured schemes (65.7%) and had a migratory history (20%). This study highlights the value of autopsy in revealing maternal mortality etiologies, showing a predominance of indirect/infectious causes and endemic diseases often missed clinically, despite PPH remaining the main direct cause. Findings reaffirm the strong link between maternal death and social/economic inequity, access barriers, and regional/migratory vulnerabilities. Effectively reducing maternal mortality necessitates rigorous clinical management, regionalized public health strategies addressing inequities, and integrating pathological data for targeted surveillance.