Streptococcus suis is a Gram-positive pathogen contributing to swine mortality and significant economic losses within the pork production industry. Zoonotic transmission to humans can also occur, leading to severe diseases and poses a global health risk. With no commercial serotype-independent vaccines available, prevention of S. suis infections depend on the use of farm-specific autogenous bacterins, offering only narrow-strain responses, which complicate effective disease management. This study aimed to develop a novel gamma-irradiated whole-cell S. suis vaccine (Gamma-SU) and evaluate its immunogenicity in murine and porcine models. Gamma-SU was genetically modified through deletion of the cpsF gene involved in capsular polysaccharide biosynthesis and modification of the gene encoding the suilysin toxin. These modifications aimed to attenuate virulence and ensure vaccine-mediated immune responses were independent of the highly variable capsule. Successful attenuation of suilysin activity was confirmed using haemagglutination and haemolysis assays. Inactivation kinetics following gamma-irradiation were characterised, and a sterilising dose suitable for vaccine manufacture was established. Structural integrity of irradiated Gamma-SU relative to live bacteria was assessed by scanning and transmission electron microscopy, as well as evaluation of innate immune activation in vitro. These studies demonstrated that Gamma-SU retained whole-cell structure and immunostimulatory capacity following irradiation. Immunogenicity was first assessed in a murine model by measuring S. suis-specific IgG and IgG subclass responses. Cross-reactivity of serum IgG against proteins from multiple S. suis serotypes was also observed. This was extended to a porcine dose-response study, which demonstrated dose-dependent induction of S. suis-specific IgG antibodies and their ability to bind the surface of encapsulated S. suis, as assessed by ELISA and flow cytometry. Collectively, our data demonstrates the potential a gamma-irradiated whole cell vaccine strategy for S. suis, supporting further development toward a broadly protective vaccine for the pork industry with potential benefits for reducing zoonotic transmission to humans.