Background: Musculoskeletal disorders (MSD) caused by occupational-related factors continue to place huge burdens on global workforces. Significant numbers of workers report potential adverse health outcomes related to the condition, such as physical injury, disability, and decline in quality of life. Occupational-related MSD also poses additional burdens to healthcare services and diminishes productivity at work. The condition usually worsens in informal sectors where the work environments are often poorly designed. This paper explored occupational and physical environmental factors that induce work-related neck and/or shoulder pains among self-employed tailors in Gondar city, Northwest Ethiopia. Methods: We conducted across-sectional survey from April to May 2019 on 422 tailors selected with systematic random sampling technique. Nordic Musculoskeletal questionnaire was used to measure pains in neck and/or shoulder, and the questionnaire was pretested and administered by interviewers. Work-related factors such as working posture, rest break, training in safety and health, and the availability of adjustable chairs at workplaces were assessed. The significance of associations was set at a < 0.05 p-value and adjusted odds ratios (AOR) with a confidence interval (CI) of 95% were used to determine strength of associations. Results: A total of 419 tailors participated with a response rate of 99.3%. The mean age and mean years of experience were 29.23 (SD ± 7.03) and 1.48 (SD ± 0.50) years, respectively. The study found that the prevalence of pain in either neck or shoulder or both sites in the last 12 months was 66.6% (N = 279) [95% CI (62.1, 71.1)]. Pains in shoulder and neck were observed in 72.1% (N = 302)[95% CI (67.8, 76.4)] and 68.3% (N = 286) [95% CI (64.0, 72.6)] of the interviewees, respectively. The majority, 78.1% (n = 218) of those with pains indicated they were prevented from doing normal daily activities. Work