In this work, we examine how strain exerted on individual ZnO nanorods (NRs) can influence the fluorescence signals that are emitted from fluorophore molecules and subsequently coupled into and guided along the NR. We elucidate the relationships between the incremental levels of compressive and tensile strain on the NRs and measured fluorescence intensity of a model fluorophore, rhodamine 6G (R6G), as a function of the position on the NRs. We reveal that compressive strain on the NRs leads to a decrease in the guided fluorescence signal, while tensile strain leads to an increase in the fluorescence intensity. Compared to an unstrained state, approximately 35% decrease (increase) in R6G fluorescence intensity was observed from ZnO NRs when they were under compressive strain of −14% (tensile strain of +10%). Further, our systematic acquisition of the incremental addition of uniaxial strain result in a linear relationship of the coupled fluorescence signal and the amount of applied strain. The degree of fluorescence intensification on nanorod ends (DoF), which is a quantitative indicator for the amount of R6G signals coupled into and waveguided to the NR ends compared to those on the main body, also exhibits a linear relationship with strain. These outcomes, in turn, demonstrate that strain alters the waveguiding capabilities of ZnO NRs in a predictable manner, which can be exploited to modulate and optimize fluorescence and other light signals emitted by a nearby source. Considering the wide utility of ZnO NRs in photonics, optoelectronics, and sensors, insights from our study may be highly valuable to effectively controlling and enhancing optical signals from chemical and biological analytes through strain.