The developments in synthetic polymer chemistry have devoted to meet the huge demand required to create efficient, high yield, and operationally simple chemical methods that can be easily adapted to macromolecular level. In this regard, thiol-based reactions have been rejuvenated since last two decades, and extensively used in polymer chemistry. Amongst, thiol-yne reactions have gained much interest owing to rapid reaction rate to produce complex macromolecular structures, such as linear/non-linear polymers, and network structures, and the reactions can proceed both in organic and aqueous media. More importantly, thiol-yne reactions can proceed through both nucleophile and radical-based route, offering a remarkable opportunity in regulating polymer synthesis for desired applications. Nowadays, nucleophilic thiol-yne reactions have been frequently utilized at the macromolecular level since the reactions are simply triggered by using a base, or proceed in a slightly basic media without requiring any external regulator (i.e. heat and light). Moreover, recent studies have shown that nucleophilic thiol-yne reactions not only allow even faster polymerization but also lead to the rapid construction of hydrogels exhibiting unique features, and preparation of dynamic bond exchange reactions based on thiolalkynone reactions. In this review article, historical developments made in the nucleophilic thiol-yne reactions have been summarized in terms of polymer synthesis, modification, and applications.