A systematic calibration approach is presented to correlate the digital output of an infrared camera and the scene temperature. Aided by the optoelectronic properties of the camera, as few as two experimental data points are needed to establish this correlation. This approach can readily include the effects of atmospheric transmission, scene emissivity, and different background subtractions. Hence, the temperature conversion in flight can be reliably obtained from laboratory calibration. The conversion function can also be used to identify the camera's thermal sensitivity and temperature resolution, which are important information in different space missions. In applying this calibration procedure to a laboratory camera and the compact thermal imager onboard the International Space Station, its validity is confirmed.