Plant vascular pathogens travel long distances through host veins leading to life-threatening, systemic infection. In contrast, non-vascular pathogens remain restricted and produce localized symptoms. The molecular requirements for microbial tissue-specific plant colonization that lead to systemic or non-systemic infection remain unclear. Here, our team aimed to define the role of CbsA, a bacterial cellobiohydrolase, for tissue-specific plant infection. We determined that CbsA acts as a phenotypic switch between vascular and non-vascular pathogenesis. CbsA expression allowed non-vascular Xanthomonas to cause vascular blight while mutation of cbsA resulted in reduced vascular or enhanced non-vascular symptom development. cbsA was enriched in genomes of xylem-colonizing, vascular bacteria in the Xanthomonadaceae family. Phylogenetic analysis further revealed that cbsA was lost in many non-vascular lineages, suggesting that vascular pathogenesis is ancestral. Our results overall demonstrate how the gain and loss of a single locus can facilitate the evolution and biology of bacterial tissue-specific plant colonization.