Ambient air pollution from PM2.5 is a major risk to human and environmental health, with significant impacts on mortality and morbidity. Mitigation policies—which may be regional or national in extent—need to consider both primary and secondary particles to be effective, balancing within-region emissions and longer-range transport phenomena. The modelling system WRF-CMAQ was used to simulate the impact of emissions reductions in the West Midlands region of the UK, evaluating the change in total PM2.5 and in its primary and secondary components. Domestic combustion, road transport and agriculture emissions were reduced individually or in combination, at a national or at local level. Combined reduction of road transport and agriculture emissions showed the strongest reduction (29%) in average PM2.5 if applied at national level. At the local level, reductions from domestic combustion were shown to be the most effective policy (13.4% on average). Secondary inorganic fractions of PM2.5 are the most abundant, with 25% NO3− 21% SO42− and 13% NH4+ on average. Scenario analysis shows that the contribution of secondary components to the fractional change of PM2.5 dominates for national policies (up to 0.86 for NO3−) when road transport and agriculture activities are reduced, while at the regional level the elemental and organic carbon fractional changes are dominant (up to 0.64 for organic carbon).