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This article compares the performances of the most commonly used keypoint detectors and descriptors (SIFT, SURF, KAZE, AKAZE, ORB, and BRISK) in keypoint-based relative radiometric normalization (RRN) of unregistered bitemporal multispectral images. The keypoints matched between subject and reference images represent possible unchanged regions and form a radiometric control set (RCS). The initial RCS is further refined by removing the matched keypoints with a low cross-correlation. The final RCS is used to approximate a linear mapping between the corresponding bands of the subject and reference images. This procedure is validated on five datasets of unregistered multispectral image pairs acquired by inter/intra sensors in terms of RRN accuracy, visual quality, quality, and quantity of the samples in the RCS, and computational time. The experimental results show that keypoint-based RRN is robust against variations in spatial-resolution, illumination, and sensors. The blob detectors (SURF, SIFT, KAZE, and AKAZE) are more accurate on average than the corner detectors (ORB and BRISK) in RRN, with an expense of higher computational cost. The source code and samples of datasets used in this study are made available at https://github.com/ArminMoghimi/keypoint-based-RRN to support reproducible research in remote sensing.