Congestion pricing is one of the widely contemplated methods to manage traffic congestion. The purpose of congestion pricing is to manage traffic demand generation and supply allocation by charging fees (i.e., tolling) for the use of certain roads in order to distribute traffic demand more evenly over time and space. This study presents a framework for large-scale time-variable congestion pricing policy determination and evaluation. The proposed framework integrates discrete departure-time choice and route choice models within a regional dynamic traffic assignment (DTA) simulation environment; creating a unified variable spatio-temporal (location- and time-specific) congestion pricing framework. The framework addresses the impact of tolling on: 1) road traffic congestion (supply side), and 2) travellers’ behaviour and choice dimensions including departure time and route choices (demand side). The framework is applied to a simulation-based case study of tolling a major freeway in Toronto while capturing the regional effects across the Greater Toronto Area (GTA). The models are developed and calibrated using regional household travel survey data that reflect the heterogeneity of travellers’ personal and socioeconomic attributes. The DTA model is calibrated using actual traffic counts from the Ontario Ministry of Transportation and the City of Toronto. The case study examined two tolling scenarios: flat and variable tolling. The results indicate that: (1) more benefits are attained from variable pricing due to departure-time rescheduling as opposed to predominantly re-routing only in the case of flat tolling, (2) widespread spatial and temporal re-distributions of traffic demand are observed across the regional network in response to tolling a significant, yet relatively short, expressway serving Downtown Toronto, and (3) variable pricing mirrors temporal congestion patterns and induces departure time re-scheduling while flat tolling causes major and counterproductive rerouting patterns, which was observed to block access to the tolled facility itself.