The Canadian prairie provinces of Manitoba, Saskatchewan, and Alberta have reported the highest human incidence of clinical cases of West Nile virus (WNV) infection in Canada. The primary vector for WVN in this region is the mosquito Culex tarsalis. This study used constructed models and biological thresholds to predict the spatial and temporal distribution of Cx. tarsalis and WNV infection rate in the prairie provinces under a range of potential future climate and habitat conditions. We selected one median and two extreme outcome scenarios to represent future climate conditions in the 2020 (2010-2039), 2050 (2040-2069) and 2080 (2070-2099) time slices. In currently endemic regions, the projected WNV infection rate under the median outcome scenario in 2050 raised 17.91 times (ranged from 1.29-27.45 times for all scenarios and time slices) comparing to current climate conditions. Seasonal availability of Cx. tarsalis infected with WNV extended from June to August to include May and September. Moreover, our models predicted northward range expansion for Cx. tarsalis (1.06-2.56 times the current geographic area) and WNV (1.08-2.34 times the current geographic area). These findings predict future public and animal health risk of WNV in the Canadian prairie provinces.