Ganirelix acetate (GAN) is a third-generation gonadotropin-releasing hormone (GnRH) antagonist with high antagonistic activity and minimal histamine-releasing properties. This synthetic decapeptide is clinically approved for inhibiting premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation. Assessing the chemical stability of GAN is crucial for optimizing its formulation, manufacturing, and storage conditions. This study investigates the forced degradation behavior of GAN following ICH Q1A(R2) and Q1B guidelines. An isocratic, mass-compatible liquid chromatography (LC) method was developed to achieve sufficient resolution between GAN and its degradation products. GAN exhibited degradation under all tested stress conditions, with significant degradation observed under alkaline (22.4%) and acidic (18.1%) hydrolysis. Four major degradation products were detected, and their putative structures were predicted based on liquid chromatography–quadrupole time-of-flight (LC-QTOF) analysis. The most prominent degradation product, DP-I, was observed under all stress conditions and predicted as Ac-D-2Nal1-D-Phe(4-Cl)2-D-3Pal3-clipped GAN, likely formed via peptide bond hydrolysis at the C-terminus. Under alkaline and acidic hydrolytic conditions, DP-II (D-Ser4 GAN) and DP-III (D-Pro9 GAN) emerged as the predominant degradation products, potentially resulting from the racemization of L-Ser4 and L-Pro9, respectively. DP-IV, although detected in trace amounts across all stress conditions, was predicted to arise from the deamidation of D-Ala10 at the N-terminus. The fragmentation pathways of GAN and its four degradation products were elucidated, and their plausible chemical structures were proposed based on MS/MS data. The results suggest that GAN is highly susceptible to acid- and base-mediated hydrolysis, followed by photolytic, oxidative, and thermal degradation. These findings provide insights into the hydrolytic and oxidative stability of GAN, supporting formulation development and the design of more stable analogues.