Employees’ innovative work behaviour can help firms’ competitiveness. Existing research focuses on several factors, including HR policies, psychological empowerment as well as manager and co-worker support, to explain innovative work behaviour. However, much of this literature analyses just one of these, neglecting how they interact and limiting our understanding of the causes of innovative work behaviour. Synthesizing this work, we develop a novel and holistic framework that examines 1) how high-involvement HR systems are linked via the mediating role of psychological empowerment to innovative work behaviour and 2) how both manager and co-worker support moderate this relationship. Analysing software companies in Pakistan, we use hierarchical linear modelling to assess this framework. We draw on a unique dataset that captures HR policies at the organizational level as well as management and co-worker support, and supervisors’ assessments of individuals’ innovative work behaviour at the individual level. We analyse specific groups of HR practices. Psychological empowerment mediates the relationship between high-involvement HR systems and employees’ innovative work behaviour. Manager and co-worker support moderate the relationship between psychological empowerment and innovative work behaviour. Motivation-enhancing HR practices have a direct effect on innovative work behaviour, whereas ability- and opportunity-enhancing ones are mediated by psychological empowerment.