Mau Forest in the upper reaches of the Mara River basin has recently undergone increased forest destruction followed by human settlement and agricultural activities. These anthropogenic activities may be contributing nutrients and heavy metals, ultimately polluting the river water and eventually Lake Victoria water hence damaging these aquatic ecosystems. This study sought to establish the effect of anthropogenic activities and season on the water quality of the Amala and Nyangores tributaries of the River Mara in Kenya. Pristine springs in the Mau Forest were used as reference sites. Water samples were analyzed for pH, temperature, conductivity, nutrients, selected heavy metals, and selenium. The mean range of the parameters measured from sites along the tributaries was pH 5.44–7.48 and that for conductivity was 20–99 μS/cm while the mean range of nutrient levels (μg/L) was 80–443 (NO3−−N), 21.7–82.7 (NH4+–N), 11.9–65.0 (soluble reactive phosphorous), and 51–490 (total phosphorous). The mean range for heavy metals and selenium (in μg/L) from sites along the tributaries were 6.56–37.6 (Cu), 0.26–4.97 (Cd), 13.9–213 (Zn), 0.35–3.14 (Cr), 0.19–5.53 (Mn), 1.90–9.62 (Pb), and 0.21–4.50 (Se). The results indicated a significant difference (p ≤ 0.05) between the reference sites and the different sampling sites, indicating that anthropogenic activities were impacting the quality of water in the two tributaries. Although most of the parameters were within the WHO (2004), USEPA (2014) and NEMA (2006) acceptable limits for surface waters, they were above the permissible levels for domestic use. Moreover, the levels of nutrients, heavy metals, and selenium were significantly higher in the wet season than in the dry season, further indicating that anthropogenic activities are causing a disturbance in the aquatic system. Therefore, further anthropogenic activities should be checked and limited so as to conserve the ecosystem.