Background School teachers constitute an occupational group which reported a high prevalence of work-related musculoskeletal disorders (WRMSDs). Different individual, occupational and psychosocial factors have been identified to influence the complex process of WRMSDs. WRMSDs represent an important and costly occupational health problem being responsible for a poor quality of life (QOL) of teachers. This study aimed to determine the prevalence, the risk factors, and the impact of WRMSDs on the QOL of teachers. Methods 310 full-time teachers from 15 public schools were surveyed using an interview questionnaire about their sociodemographic and occupational characteristics, the Nordic Musculoskeletal Questionnaire and the SF-36 Health Survey (SF-36). Results Self-reported prevalence of WRMSDs at any body part over the past 12 months among teachers was 66.77%. Neck pain (56.1%) was the most prevalent WRMSD followed by shoulders (53.2%), low back (53.2%) and knees (50.6%) pain. Female gender, body mass index, the number of students per classroom, the number of classes per week, different adapted awkward postures and the lack of enough supervisor’s psychological support at work were among the risk factors positively associated with WRMSDs. WRMSDs had a negative impact on the physical and mental QOL of teachers with WRMSDs as reflected by their lower scores on all scales of the SF-36 compared to their counterparts without WRMSDs (p ˂ 0.05). Conclusion WRMSDs were a highly prevalent problem among teachers in Cairo, Egypt and negatively influencing their physical and mental QOL. Different individual, occupational and psychosocial factors had been shown to be significant predictors for the occurrence of WRMSDs reflecting their complex nature and multifactorial etiology.