Wavefront estimation from the slope-based sensing metrologies zis important in modern optical testing. A numerical orthogonal transformation method is proposed for deriving the numerical orthogonal gradient polynomials as numerical orthogonal basis functions for directly fitting the measured slope data and then converting to the wavefront in a straightforward way in the modal approach. The presented method can be employed in the wavefront estimation from its slopes over the general shaped aperture. Moreover, the numerical orthogonal transformation method could be applied to the wavefront estimation from its slope measurements over the dynamic varying aperture. The performance of the numerical orthogonal transformation method is discussed, demonstrated and verified by the examples. They indicate that the presented method is valid, accurate and easily implemented for wavefront estimation from its slopes.