A monolithic CMOS image sensor based on the pinned photodiode (PPD) and optimized for X-ray imaging in the 300 eV to 5 keV energy range is described. Featuring 40 μm square pixels and 40 μm thick, high resistivity epitaxial silicon, the sensor is fully depleted by reverse substrate bias. Backside illumination (BSI) processing has been used to achieve high X-ray QE, and a dedicated pixel design has been developed for low image lag and high conversion gain. The sensor, called CIS221-X, is manufactured in a 180 nm CMOS process and has three different 512×128-pixel arrays on 40 μm pitch, as well as a 2048×512 array of 10 μm pixels. CIS221-X also features per-column 12-bit ADCs, digital readout via four highspeed LVDS outputs, and can be read out at 45 frames per second. CIS221-X achieves readout noise of 2.6 e- RMS and full width at half maximum (FWHM) at the Mn-K_α 5.9 keV characteristic X-ray line of 153 eV at -40 °C. This paper presents the characterization results of the first backside illuminated CIS221-X, including X-ray response and readout noise. The newly developed sensor and the technology underpinning it is intended for diverse applications, including Xray astronomy, synchrotron, and X-ray free electron laser light sources.