Artisanal and small-scale gold mining (ASGM) is the single largest intentional-release of mercury (Hg) in the world. In Cameroon, there is paucity of data concerning the contribution of ASGM to human mercury contamination. This study aimed at providing new data for a region in Cameroon where ASGM is practiced, through an assessment of the concentration of total mercury (T-Hg) in hair as a function of occupational exposure, and investigating symptoms related to Hg toxicity. A quantitative cross-sectional survey design was employed involving 60 gold miners from four gold mining districts: Batouri, Kette, Ngoura and Bétaré-Oya. Questionnaire was used to collect sociodemographic data, nature of work processes and symptoms of Hg toxicity. Scalp hair samples were drawn from all 60 respondents and analysis for total mercury (T-Hg) in hair was done via a milestone DMA-80 Mercury Analyzer. The results show that males (86.7%) were generally represented than females (13.3%). The minimum, maximum and mean concentrations of Hg in hair of miners across the four districts was 0 µg/g, 8.97 µg/g and 2.09 ± 1.84 µg/g respectively. Over three-quarters (71.7%) of the miners had T-Hg in hair above the occupational toxic threshold of 1 µg/g set by the United States Environmental Protection Agency (USEPA), also identified as 66.7% in the “alert level” and 5% as “high” according the German Human Biomonitoring (HBM) Commission. The factors affecting the concentration of mercury in hair according to a multiple linear regression model (R2 = 0.400 and p = 0.03) were living in Bétaré-Oya, younger age, male sex, burning of amalgam, and increased number of working days per week. According to the same model (R2 = 0.076 and p = 0.940), the symptoms associated with mercury exposure were unusual tiredness, excessive sleeping, dizziness and visual difficulties. ASGM in the east region of Cameroon, therefore, is significantly contributing to Hg contamination in humans as a result of occupational exposures to Hg, and there is urgent need for interventions to mitigate human exposure, especially as adverse health effects cannot be excluded following long-term exposures.