Background: One of the main occupational diseases among dentists is musculoskeletal disorders (MSDs). Their quality of life and productivity at work might become negatively affected by these issues. Aim of the study: to ascertain the frequency of MSDs among primary care dentists and assess their effect on the dentists' quality of life. Setting: This cross-sectional study was conducted on different primary healthcare centers (PHCs) in Menoufia governorate. Sampling: 170 dentists were chosen by convenient sampling while the PHCs were selected by multistage random sampling. Tools: A predesigned questionnaire included sociodemographic and occupational information as well as two scales—the Standardized Nordic questionnaire for MSDs and the WHO shortened form for quality of life. Results: MSDs were present in 148 (87.1%) of the 170 dentists in this study, with the majority occurring in the neck, shoulders, and lower back (67.1%, 58.2%, and 57.6%, respectively). The occurrence of MSDs was associated with age, body mass index, years of experience, weekly working hours, and longstanding (adjusted OR: 1.48, 1.17, 1.25, 2.27, and 2.75, respectively). The mean overall score of quality of life and its four domains was lower for those with MSDs than for those without. A higher BMI and a greater number of MSD sites were poor indicators of quality of life. Conclusion and Recommendations: According to this study's findings, the dentists' quality of life was affected by their approximately high level of MSDs. Therefore, it is crucial to adopt a health education program that includes ergonomic regulations to avert these conditions.