Several recent surges in COVID-19 cases due to newly emerging variant strains of SARS-CoV-2 with greater transmissibility have highlighted the virus’s capability to directly modulate spike-ACE2 interactions and promote immune evasion by sterically masking the immunogenic epitopes. Recently, there have also been reports of the bidirectional transfer of coronavirus between different animal species and humans. The ability of coronavirus to infect and adapt to a wide range of hosts can be attributed to new variants that modify the molecular recognition profile of the spike protein (S protein). The receptor-binding domain of the spike protein specifically interacts with key host receptor molecules present on the host cell membranes to gain entry into the host and begin the infection cycle. In this review, we discuss the molecular, structural, and functional diversity associated with the coronavirus receptors across their different phylogenetic lineages and its relevance to various symptomatology in the rapid human-to-human infection in COVID-19 patients, tropism, and zoonosis. Despite this seeming diversity of host receptors, there may be some common underlying mechanisms that influence the host range, virus transmissibility, and pathogenicity. Understanding these mechanisms may be crucial in not only controlling the ongoing pandemic but also help in stopping the resurgence of such virus threats in the future.