Lake Ziway, a freshwater lake located in Ethiopia, is under the pressure of pesticide and nutrient pollution due to agricultural activity and urbanization. This study has analysed concentrations of insecticides, fungicides and nutrients in water and sediment samples of Lake Ziway taken in the wet and dry season at 13 sites expected to be under different environmental stress and assessed their expected ecological impacts. Malathion, dimethoate, metalaxyl, diazinon, chlorpyrifos, fenitrothion and endosulfan were detected in more than half of the water samples, while diazinon, α-cypermethrin and endosulfan were frequently detected (>25%) in sediment samples. Higher levels of physicochemical parameters were observed at sample locations proximate to agricultural and urban activities. Risk quotients (RQ) and multi-substance Potentially Affected Fraction (msPAFRA) were calculated to assess the ecological risk of individual and mixture of pesticides, respectively. The majority of the pesticides detected in the water of the lake showed a potential acute risk (RQ > 1), specifically the insecticides chlorpyrifos, λ-cyhalothrin and α-cypermethrin for which high potential acute risks were calculated using a 2nd tier risk assessment. Levels of pesticides in sediment showed low ecological risks. Arthropods and fishes are expected to be highly affected by mixtures of pesticides (msPAFRA = < 1–80%) detected at locations that are proximate to smallholders’ farms, and receive largescale farms’ wastewater and at sites where inflow rivers join the lake. Macroinvertebrates based redundancy analysis showed the effectiveness of EPT richness to assess ecological status of the lake. Training for smallholder farmers on pesticides safety and usage, and implementation of improved effluent management mechanisms by floriculture farms are urgently needed intervention measures to reduce the pollution.