Quality data on the magnitude and determinants of work-related injuries is an important element in the development of appropriate preventative strategies. However, there have been many challenges in obtaining quality information on work-related injuries in the developing countries. This archival study based on the data from workers’ compensation registry from the year 2016 to 2019 aimed at determining trends and factors associated with work-related injuries (WRI). Data from 4578 WRI claims reported to Workers Compensation Fund (WCF) in Tanzania were analyzed. As expected, this new workers’ compensation system had increasing participation from inception in 2016 through 2019, resulting in increasing numbers of fatal and non-fatal work-related claims. Motor traffic accidents, machine faults and falls were the most reported causes of WRI. Males had more than 2-fold increased odds of sustaining fatal injuries compared to females. More than 6-fold increased odds of fatal injuries were observed for injuries occurring during conveyance. Explosions, motor traffic accidents, and falls were more likely to result into fatal injuries. Increased odds of fatal injuries were observed in workers from transportation and storage sector; information and technology; construction and building; and electricity, gas, and steam sectors, as well as among teachers, drivers, office workers, and security guards. The current study offers some insights regarding trends and associated factors that are vital in planning and implementation of appropriate preventative strategies for work-related injuries in Tanzania.