The study aimed to assess concentration of some heavy metals and physico-chemical parameters in relation to water quality and zooplankton Lake Langano. The lake was sampled at four stations from January to July, 2016 concurrently with physico-chemical parameters, heavy metals concentration and zooplankton. The data was analyzed using descriptive statistics, ANOVA, canonical correspondence and biological indices. 21 zooplankton species with eight species of cladocera and four species of cyclopoid copepods were identified from the lake. The diversity index narrowly ranged from 0.39-0.77 spatially. The abundance of zooplankton was maximum during April month at all sites with statistically significant variation both temporally and spatially (p<0.05). The abundance and species composition of zooplankton of the lake was negatively correlated Zn, Cu, Cd, PO43-, NO3-, conductivity and water temperature. A maximum (189. 05±32.05mg/l and 72.67±125.21mg/l) of concentration of Cd was measured temporally and spatially respectively and that exhibited temporal significant difference (p < 0.05). High (27.85 ± 4.970C) mean value of water temperature was measured at Simbo site that showed temporally significant variation (p<0.05). The maximum mean TDS, NO3- and PO43- of Simbo site (855.29±42.67mg/l, 29.44±32.74mg/l and 0.40±0.67mg/l) and no statistically significantly varied spatially (p>0.05). Most of the concentration of physico-chemical parameters and heavy metal of the lake were above the permissible limits set by WHO and EPA. The study provided baseline information on some water chemistry and biota of the lake and their ecology of Lake Langano.