The current study elucidates the stress degradation behavior of donepezil HCl, a medication used to treat Alzheimer-type dementia. Using hydrolytic, oxidative, thermal, and photolytic conditions, the forced degradation investigation was conducted in accordance with ICH recommendations. In neutral hydrolysis, oxidative, thermal, and photolytic conditions, donepezil is comparatively stable; nevertheless, significant degradation was noted in acid and base hydrolysis. Using sophisticated analytical methods such as LCMS, Preparative-HPLC, NMR, and HRMS, the degradation products were identified, isolated, and their structural validity was confirmed. Degradation products 1, 2, and 3 are the three degradation products that were found and isolated during acid degradation. Conversely, products 1 and 3 generated during base hydrolysis degradation. Degradation product 1 and 3 were known products, while degradation product 2 is new compound that have not yet been documented. Using an advanced analytical approach, this is the first recorded comprehensive structural characterization of all degradation products. In the current work, high-resolution mass spectroscopy and nuclear magnetic resonance spectroscopy were employed to get specific confirmation of degradation product structures. In the future, degradation products with lower runtime will also be identified using the present LCMS technique.