Road traffic exhaust emission predictions are used to inform transport policy and investment decisions aimed at reducing emissions and achieving sustainable mobility. Emission predictions are also used as inputs when modelling air quality and human exposure to traffic-related air pollutants.To be effective, such policies and/or integration must be based on robust models that not only provide point-based predictions, but also inform these with an interval of confidence that properly accounts for the propagation of uncertainties through the complex chain of models involved. This paper develops a data-driven methodological framework which enables calculating the uncertainty in average speed-based emission predictions induced by uncertainty in its traffic data inputs which are most often predictions (or outputs) of traffic flow models. An ensemble-based optimisation approach is used to estimate both calibration and validation errors arising from uncertainty in the structure and parameterisation of the Cell Transmission Model (CTM); a discretised first-order macroscopic traffic flow model that is often integrated with average speed-based emission models. A Monte Carlo sampling approach is proposed to propagate the uncertainty in traffic flow inputs to emission predictions. To ensure transferability of findings, this methodology has been tested using multiple real data sets on three motorway road networks, one of which operates under Variable Speed Limits (VSL).