Background: Occupational diseases represent a significant global public health challenge, yet reliable data from transitioning economies remain limited. This study aimed to analyze newly confirmed occupational disease cases in Mongolia over a 50-year period (1975–2023), identifying long-term trends and the prevalence of leading disease categories. Methods: A retrospective, record-based study was conducted using quantitative data from 10,233 officially confirmed and compensated cases of occupational diseases resulting in an officially certified loss of labor capacity. Incidence rates per 100,000 workers were calculated for the 1992–2023 period. Leading diseases were classified by organ system, with focused analyses on respiratory diseases, occupational poisonings, and neurological disorders. Results: Dust- and particulate-induced respiratory diseases accounted for the largest proportion of cases (57.4%), followed by occupational neurological disorders (16.2%) and occupational poisonings (8.0%). From 1992 to 2023, incidence rates among male workers were consistently 3–7 times higher than those among female workers. Analysis of exposure duration showed mean durations of 13.6 ± 4.9 years for silicosis (J62) and 20.7 ± 10.7 years for inorganic substance poisoning (T57). While respiratory diseases were predominant historically, occupational neurological diseases demonstrated an increasing trend after 2015. Conclusions Occupational neurological disorders are showing an increasing trend in Mongolia, reflecting a shift in the national occupational disease pattern. However, as the registry is based on the national compensation framework, these findings likely reflect recognized cases rather than the true epidemiological incidence, suggesting potential underreporting. Strengthening surveillance beyond the compensation system and improving diagnostic capacity for a broader range of work-related conditions are essential for effective prevention and policy development.