Mooring observations in the James River estuary show one-cell lateral circulation that persists from spring to neap tides despite large changes in vertical stratification. The lateral circulation is twice as strong on ebb than on flood during neap tide, but shows little flood-ebb asymmetry during spring tide. A numerical model is developed to simulate the lateral circulation. It captures an observed three-fold change in stratification and reproduces the observed temporal evolution of the lateral circulation. An analysis of the streamwise vorticity equation reveals that the lateral circulation is generated by the tilting of the planetary vorticity by the along-channel flow but opposed by turbulent diffusion and lateral baroclinic forcing due to sloping isopycnals. Tilting of the vertical component of relative vorticity by the along-channel flow is insignificant. Vortex stretching is also weak in the straight segment of the estuary where mooring observations were available. During neap tide, vorticity generation is larger on ebb due to stronger vertical shear in the along-channel current, thereby leading to stronger lateral circulation on ebb. During spring tide, however, turbulent mixing reduces the shear and the flood-ebb asymmetry in the vorticity generation, resulting in little flood-ebb variations in the lateral circulation strength. Such strength is comparable between spring and neap tides because of the compensative changes in the vorticity budget: increased baroclinic forcing and decreased diffusion during neap tides versus decreased baroclinic forcing and increased diffusion during spring tides.