ABSTRACT The ecological and health risks posed by heavy metals (HMs) have been a major concern of the world. This study aimed to assess the potential health and ecological risks of Fe, Pb, Cr, Zn, Co, Ni, and Cd metals in the sugarcane and its growing soil at Sanka farmland, Northeast Ethiopia. The sampling was conducted at six locations in three potential sugarcane cultivation Kebeles. HMs were quantified using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). They were found in the range of 2297 (Fe) to 3.750 (Co) mg/kg for soil and 0.557 (Fe) to 0.020 (Zn) mg/L for sugarcane. The metal transfer factors of the investigated HMs were 0.0002 (Fe) to 0.384 (Co), indicating a low sugarcane response to HMs. Six pollution indices (three multi-metal ecological impact indicators and three single-metal ecological effect indicators) were applied to the data. All multi-metal ecological impact indicators show that the soil is severely polluted. In contrast, the single-metal ecological effect indicators showed severe pollution by Fe and Cd, moderate pollution by Pb and Cr, and low pollution levels by Ni, Co and Zn. Apart from Cd, Cr and Pb in the soil sample and Zn and Cd in the sugarcane juice sample, all HMs concentrations were below allowable limits set by World Health Organization (WHO). The contribution of each exposure route to the total intake of HMs showed the trend of non-dietary oral intake > dermal contact > juice drinking > inhalation route. Single-metal health risk assessment (hazard quotient) revealed no significant non-carcinogenic risk for adults and children, while multi-metal health risk assessment (hazard index) indicated children have high non-cancer risks. Similarly, the single-metal cancer risk assessment showed no cancer risk, except Cr, whereas the multi-metal cancer risk assessment showed children and adults inhabitants likely to have cancer in their lifetime.