Hexachlorocyclohexane (HCH), an organochlorine pesticide imposes several harmful impacts on the ecosystem. β- and δ-isomers of HCH are highly toxic, persistent, and recalcitrant to biodegradation, slow and incomplete degradation of β- and δ- isomers have been reported in a few strains. We have isolated a strain designated as Sphingopyxis strain MC4 that can tolerate and degrade high concentrations of α-, β-, γ- and δ-HCH isomers. To date, no other Sphingopyxis strain has been reported to degrade β- and δ-isomers. To understand the underlying genetic makeup contributing to adaptations, the whole genome of strain MC4 was sequenced. Comparative genome analysis showed that strain MC4 harbors the complete pathway (lin genes) required for HCH degradation. Genetic footprints such as presence of lin genes on genomic islands, IS6100 elements in close proximity of lin genes, and synteny in lin flanking regions with other strains reflects the horizontal gene transfer in strain MC4. Positive selection and HGT drive the adaptive evolution of strain MC4 under the pressure of HCH contamination that it experienced in its surrounding niche. In silico analyses showed efficient binding of β- and δ-isomers with enzymes leading to rapid degradation that need further validation by cloning and biochemical experiments.