Background: The impact of work-related musculoskeletal symptoms (WMSS) permeates various occupations. Objective: To compare WMSS and associated risk factors among domestic gas workers (DGWs) and staff of Works Department (SWD) in Enugu. Methods: One-hundred adults (DGW = 50, SWD = 50) participated in this cross-sectional study. The Nordic Musculoskeletal Questionnaire and a demographics questionnaire were used to assess the prevalence of WMSS and related risk factors. Data were analysed using independent t-test or Mann-Whitney U, chi-square, and logistic regression at p < 0.05. Results: The DGWs (86%) had a significantly (χ2 = 24.45, p < 0.001) higher WMSS than the SWD (38%). Lower-back (54%) and shoulder (52%) were the most affected body parts among the DGWs in comparison to the hips/thighs (20%) among the SWD. Work-related factors such as daily work-duration (χ2 = 75.44, p < 0.001), lifting training (χ2 = 96.24, p < 0.001), and use of personal protective equipment (PPE) of facemask (χ2 = 100.0, p < 0.001) and gloves (χ2 = 96.09, p < 0.001) were significantly associated with general WMSS among the DGWs. However, diastolic blood pressure (DBP) (OR = 1.29, p = 0.018), work duration > 8 h/day (OR = 0.001, p = 0.028), female gender (OR = 6.98-10.26, p < 0.05), sleep duration < 6 h/day (OR = 0.56-0.73, p < 0.05) and poor exercise behaviour (OR = 0.15, p = 0.013) were the identified independent risk factors of WMSS among DGWs, while DBP (OR = 0.99, p = 0.012) and female gender (OR = 6.47, p = 0.032) were the only identified independent risk factors for SWD.