Bovine trypanosomiasis is a debilitating cattle disease caused by unicellular protozoan parasites of the genus Trypanosoma; and it is considered as a bottleneck to sufficient food production and economic growth of sub-Saharan countries including Ethiopia. A cross-sectional study was carried out from November 2020 to April 2021 in Jawi district of Northwest Ethiopia to estimate the prevalence of bovine trypanosomiasis, determine the apparent density (AP) of tsetse flies, identify the potential risk factors, and assess economic impact of the disease. For the parasitological study, immediately after recording potential risk factors, blood samples were collected from 384 randomly selected zebu breed cattle and examined using the buffy coat technique and Giemsa-stained thin smears. For the entomological survey, a total of 60 monoconical traps were deployed in two randomly selected kebeles. For economic impact assessment, economic data were collected using comprehensive and pre-tested structured questionnaire administered to 100 randomly selected households through interview. The overall prevalence of trypanosomiasis was 9.11% (95% CI= 6.43–12.45). The trypanosome species identified were Trypanosoma congolense (57.14%, n = 20), T. vivax (37.14%, n = 13) and mixed infection of T. congolense and T. vivax (5.72%, n = 2). There was statistically significant association (p < 0.05) between age and body condition score (BCS) of cattle and trypanosome infection, but no statistically significant differences were observed for sex, coat color, altitude and kebele (p > 0.05). The mean packed cell volume (PCV) value of infected group (22.46±2.56) was significantly (P < 0.001) lower than non-infected (27.77±2.22) group of animals. A total of 154 flies were captured, 110 tsetse and 44 other biting flies (Stomoxys, n=26 and Tabanus, n=18). The species of tsetse identified was Glossina tachinoides, and the apparent density was 0.61flies/trap/day. The overall economic losses per household and per individual cattle were US$ 1,644.77 and US$ 111.13, respectively. The overall mortality rate was 7.7%, and the largest