Bacterial two-component systems (TCS) are versatile signaling mechanisms that govern cellular responses to diverse environmental cues. These systems rely on phosphoryl-group transfers between histidine- and aspartate-containing modules of sensor histidine kinase and response regulator proteins. TCS diversity is shaped by the ecological niche of the bacterium, resulting in significant population-level variations. Consequently, orthologous TCSs can display considerable divergence throughout the signaling process. Here, we venture into the mechanisms governing the emergence of TCS variation, and explore the adaptation of orthologous TCS in bacteria with dissimilar lifestyles. The peculiar features of the bacterial adaptive response A/ultraviolet light repair Y (BarA/UvrY) and anoxic redox control B/anoxic redox control A (ArcB/ArcA) and their ortholog TCSs illustrate the remarkable capacity of TCSs to evolve and finely tune their signaling mechanisms, effectively addressing specific environmental challenges.