Perceived high-performance work systems (HPWS) have presented mixed results related to subjective well-being. Additionally, there remains a lack of an integrative analysis of the relationship between work–family balance and these practices. To explore this relationship more fully, we developed and tested a model that proposed work–family balance and well-being at work as mediators. Data gathered from 218 participants employed in a city council with different occupations indicated a positive relationship between perceived HPWS and work-to-family enrichment and a negative relationship between perceived HPWS and work-to-family conflict. More interestingly, based on Conservation of Resources theory and on Job-Demands Resources, the results also indicated the presence of a serial mediation model where work–family balance and well-being at work act as mediators of perceived HPWS and subjective well-being.