<p>Introduced 75 years ago, the Prisoner’s Dilemma (PD) game has been widely used to study the evolution of cooperation. In its classic form, which assumes uniform interaction rates and interaction times, cooperation is not evolutionarily viable because defection is always more profitable for individuals. This prediction contradicts empirical observations of cooperative behavior, particularly in mutualisms. In nature, mutualistic interactions do not occur randomly, and cooperating partners may evolve mechanisms or strategies to avoid interacting with low-quality partners or cheaters. In this article, we investigate the influence of non-uniform interaction rates on the evolutionary outcome of both the symmetric and asymmetric PD games, using explicit non-instantaneous pairing dynamics. In the symmetric version, cooperation is promoted by a lower cooperator–defector interaction rate, a higher cooperator–cooperator interaction rate, or a higher defector–defector interaction rate, highlighting the importance of cooperators interacting preferentially with one another. In the asymmetric version, the same pattern emerges: cooperation in both species is promoted by low interaction rates between cooperators and defectors. These results underscore the key role of non-uniform interaction rates in shaping evolutionary predictions in matrix games.</p>