The pixel size of a charge-coupled device (CCD) camera plays a major role in the image resolution, and the square pixels are attributed to the physical anisotropy of the sampling frequency. We synthesize the high sampling frequency directions from multiple frames acquired with different angles to enhance the resolution by 1.4 × over conventional CCD orthogonal sampling. To directly demonstrate the improvement of frequency-domain diagonal extension (FDDE) microscopy, lens-free microscopy is used, as its resolution is dominantly determined by the pixel size. We demonstrate the resolution enhancement with a mouse skin histological specimen and a clinical blood smear sample. Further, FDDE is extended to lens-based photography with an ISO 12233 resolution target. This method paves a new way for enhancing the image resolution for a variety of imaging techniques in which the resolution is primarily limited by the sampling pixel size, for example, microscopy, photography, and spectroscopy.