Bacterial populations communicate using quorum-sensing (QS) molecules and switch on QS regulation to engage in coordinated behaviour such as biofilm formation or virulence. The marine fish pathogen Vibrio anguillarum harbours several QS systems, and our understanding of its QS regulation is still fragmentary. Here, we identify the VanT-QS regulon and explore the diversity and trajectory of traits under QS regulation in Vibrio anguillarum through comparative transcriptomics of two wildtype strains and their corresponding mutants artificially locked in QS-on (ΔvanO) or QS-off (ΔvanT) states. Intriguingly, the two wildtype populations showed different QS responses to cell density changes and operated primarily in the QS-on and QS-off spectrum, respectively. Examining 27 V. anguillarum strains revealed that ~11% were QS-negative, and GFP-reporter measurements of nine QS-positive strains revealed a highly strain-specific nature of the QS responses. We showed that QS controls a plethora of genes involved in processes such as central metabolism, biofilm formation, competence, T6SS, and virulence properties in V. anguillarum, with large strain-specific differences. Moreover, we demonstrated that the QS state is an important driver of virulence towards fish larvae in one of two V. anguillarum strains. We speculate that infections by mixed-strain communities spanning diverse QS strategies optimize the infection efficiency of the pathogen.