Background: Teachers have the highest musculoskeletal disorders (MSD) rates worldwide because of stressful working conditions. MSD is likely to be linked to psychosocial elements such as need for social help, loss of job control, performance concerns, repetitive work, and feeling burdened and stressed. Objectives: To determine the prevalence and anatomical distribution of MSDs and the associated psychosocial risk factors, primarily depression, among female teachers in the Riyadh region of Saudi Arabia. Settings and Design: An observational, quantitative, cross-sectional study was done. Material and Methods: Data was collected from female teachers in Riyadh region, Saudi Arabia, via a questionnaire. All the participants completed the Patient Health Questionnaire (PHQ-9) and Nordic Musculoskeletal Questionnaire (NMQ). The data was analyzed using Statistical Package for the Social Sciences software. Results: Of the 372 questionnaire responses obtained from the teachers, the prevalence of depression was 65.6% and of MSD was 86%. The main site of pain was the neck (62.9%), followed by the lower back (53.8%). There was a significant relationship between the prevalence of MSD and the prevalence of depression. MSD occurred in 64.1% of participants without depression, in 95.9% of those with mild depression, and in 100% of those with more severe depression ( P ≤ 0.001). Conclusions: A high prevalence of MSD pain was found among the female teachers, especially among older women, those teaching at elementary schools, and those with a higher number of pregnancies. The coexistence of MSD and depression affects the work ability of the teachers and reduces their efficiency.