Effective weed management is crucial for optimizing horticultural and agricultural plant production. This study aims to establish a reproducible and comparable experimental protocol to determine the damage thresholds of weeds subjected to high-energy, coherent laser radiation. The lethal dose is influenced by process parameters, including plant species, growth stage, irradiation point, process precision, and laser wavelength. Recognizing the importance of adapting process parameters to specific use cases in laser weed management (LWM), this research contributes to enhancing the reproducibility and comparability of dose-response analysis for LWM applications. The study focuses on two plant species: Alopecurus myosuroides (ALOMY) and Amaranthus retroflexus (AMARE). The resulting protocol is a three-stage protocol including classification, parameter study, and detailed measurements. A key methodological insight is the necessity of a two-step parameter study: the first step involves capturing a full range of the sigmoid response curve, while the second focuses on dense sampling around the inflection point to ensure robust data fitting.