Chemokines receptors have emerged as important drug targets for development of agents against the HIV/AIDS pandemic. With the purpose of designing new chemical entities with enhanced antagonistic potencies against the CCR5 chemokine receptor, the QSAR study carried out on 70 novel phenoxybenzyl derivatives as antagonists of CCR5 HIV co receptor is presented. The developed model was validated by standard QSAR parameters and through a detailed structural analysis on how it reproduces the quantitative differences observed in the experimentally known activity data. The model showed a good correlative and predictive ability having a cross validated correlation co-efficient (r2cv) of 0.708 and a conventional correlation coefficient (r2) was found to be 0.805. The study revealed that the CCR5 antagonistic activity exhibited by the series is largely explained by steric factors of substituents emphasizing the role of size and shape of the inhibitors in making effective antagonist-CCR5 binding chemistry. A detailed investigation was made on the structural basis for the antiretroviral activity and the insights gleaned from the study could be usefully employed to design antagonists with a much more enhanced potency and selectivity.