A general model that predicts single-phase creeping flow pressure drop in microchannels of a noncircular cross section under slip and no-slip regimes is proposed. The model accounts for gradual variations in the cross section and relates the pressure drop to geometrical parameters of the cross section, i.e., area, perimeter, and polar moment of inertia. The accuracy of the proposed model is assessed by comparing the results against experimental and numerical data collected from various studies in the literature for a wide variety of cross-sectional shapes. The suggested model can be used for the design and optimization of microsystems that contain networks of microchannels with noncircular cross sections resulting from different fabrication techniques.