Purpose Achieving organizational-level outcomes through human resource practices (HRP) as the basis of nearly all organizational improvements has remained relatively unexplored, which requires more investigations. Therefore, the present study aimed to develop a framework to theorize how high-performance work systems (HPWS) can provide organizations with critical instruments for organizational learning (OL) creation that in turn leads to innovation performance (IP). Design/methodology/approach Survey-based, multisource research was designed to examine the proposed model, using the data collected from 154 pharmaceutical industry-related companies. Findings According to the study results, HPWS concentrating on enhancing practices of abilities, motivations and opportunities (AMO) were positively associated with OL, which could in turn improve IP. Moreover, innovation culture (IC) showed a significant moderating effect on the association between OL and IP. Originality/value The central originality of this research first is that HPWS acts as antecedents of OL capabilities contributing to firm-level IP; second, the relationship between OL and firm IP is contingent upon the level of IC in organizations.