Abstract Passive microwave sounders are critical for accurate forecasts from numerical weather prediction models. These sensors are calibrated using a traditional two-point approach, with one source typically a free-space blackbody target and the second a clear view to the cosmic microwave background, commonly referred to as “cold space.” Occasionally, one or both of these calibration sources can become corrupted, either by solar/lunar intrusion in the cold space view or by thermal instability of the blackbody calibration source. A Temporal Experiment for Storms and Tropical Systems (TEMPEST) microwave sounder instrument is currently deployed on the International Space Station (ISS) for a 3-yr mission. TEMPEST is also calibrated using a blackbody target and cold space view; however, the cold space view will be routinely obstructed by objects present on the ISS. Here we test an alternative single-point calibration methodology that uses only the blackbody calibration target. We find the brightness temperature difference between this new approach and the traditional two-point calibration approach to be <0.1 K when applied to 3 years of the TEMPEST CubeSat Demonstration (TEMPEST-D) mission data from 2018 to 2020. This approach is applicable to other microwave radiometers that experience occasional degradation of calibration sources, such as thermal effects, intrusions, or instability of noise diodes. Significance Statement Cross-track microwave sounders have relied on two distinct calibration sources, often the cosmic microwave background using a clear view to cold space and an ambient blackbody target. We have tested an alternative approach that uses a single calibration target, making the sensor robust to occasional field-of-view intrusions of the space view or alternatively simplifies the spaceborne sensor design by eliminating the need for a clear view to space. We find that the performance difference between this new approach and the traditional two-calibration source approach is indistinguishable for both microwave temperature/water vapor profiling and precipitation-rate estimation. This calibration technique can be applied to past, current, and future microwave sounders to help diagnose systematic uncertainties in sensor calibration targets.