Based on the first and second thermodynamic laws, a new systematic approach to study in detail the effect of fouling on the thermodynamic performance of forced convective heat transfer through a duct with constant wall temperature and constant wall heat flux for thermally and hydrodynamically fully developed turbulent flow is investigated. When considering fouling exists inside the duct, the local and mean exergy variation coefficient, exergy variation flux, dimensionless exergy variation number and the equation of exergy variation rate of working fluids, etc. have been put forward and their generalized expressions derived. A criterion evaluating the effect of fouling on the exergy variation of working fluids of the forced convective heat transfer process, which is defined as the exergy variation degradation rate, has been put forward. By reference to a duct, the numerical results of the exergy variation of working fluids are obtained (considering fouling or not), the effects of Reynolds number, the thickness of the fouling layer, dimensionless inlet temperature difference and wall heat flux on the exergy variation of working fluids are discussed. The results show that the exergy variation degradation rate increases with the increase of Reynolds number and decreases with the increase of dimensionless inlet temperature and wall heat flux. The exergy variation caused by the heat conduction of fouling plays an important role in the total exergy variation of working fluids.