The core objective of this analytical study was to develop a simple, green, and efficient high-performance liquid chromatography-diode array detector (HPLC-DAD) method for analyzing Tulathromycin (TUL) in pure powder and injection solution without the need for complex derivatization procedures. A simple liquid mobile solution of 15 mL of phosphate buffer (pH = 7.5) and 85 mL of methyl alcohol was passed through a Hypersil BDS C18 (4.6 mm × 25 cm, 5µ) stationary phase in an isocratic mode. The flow speed was controlled at 1.0 mL/min, and the DAD detector was adjusted at 210 nm because of the extremely weak UV absorption characteristic of TUL. TUL was well separated and quantified in 10 min. The HPLC-DAD forced degradation assay was carried out in dissimilar stressful environments concerning international conference for harmonization (ICH) protocols. TUL was linearly quantified from 1000.0 to 3000.0 µg·mL−1. The moderate sensitivity of the HPLC-DAD is attributed to the aliphatic, less conjugated chemical structure of TUL. The maximum degradation ratios occurred in acidic and oxidative environments with proportions of 20.11 % and 18.87 %, respectively. Furthermore, the eco-friendly merits of the HPLC-DAD method were confirmed via the application of two greenness approaches, specifically the analytical greenness tool (AGREE) and the green analytical procedure index (GAPI). The seven green subdivisions in the GAPI pictogram and the total score of 0.72 in the AGREE pictogram illustrate the greenness appraisal of the RP-HPLC-DAD stability method. The innovative RP-HPLC–DAD method is the first sustainable stability-demonstrating assay for TUL in the co-existence of its degradation products in variable stressful environments.