The isotropy of the late Universe is an assumption greatly used in astronomy. However, many studies have recently reported deviations from isotropy with a definitive conclusion yet to be made. New, independent methods to robustly test the cosmic isotropy are of crucial importance. In this work, we investigate the directional behavior of the X-ray luminosity-temperature ($L_X-T$) relation of galaxy clusters. A tight correlation exists between the luminosity and temperature of the X-ray-emitting intracluster medium. While the measured luminosity depends on the underlying cosmology, the temperature can be determined without any cosmological assumptions. By exploiting this property one can effectively test the isotropy of cosmological parameters over the full extragalactic sky. Here, we used 313 homogeneously selected X-ray galaxy clusters from the MCXC catalog and obtained core-excised temperatures for all of them. We find that the behavior of the $L_X-T$ relation heavily depends on the direction of the sky. Strong anisotropies are detected at a $sim 4sigma$ level toward $(l,b)sim (280^{circ}, -20^{circ})$. Several X-ray and cluster-related effects that could potentially explain these anisotropies were examined, but none did so. Interestingly, two other available cluster samples appear to have a similar behavior throughout the sky, while being fully independent of each other and our sample. Performing a joint analysis of the three samples, the final anisotropy is further intensified ($sim 5sigma$), toward $(l,b)sim (303^{circ}, -27^{circ})$, which is in good agreement with other cosmological probes. This result demonstrates that X-ray galaxy cluster studies that assume perfect isotropy can produce strongly biased results whether the underlying reason is cosmological or related to X-rays. The identification of the exact nature of these anisotropies is therefore crucial.
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