This study investigated the effects of the Job Demand-Control (JD-C) Model and the Effort-Reward Imbalance (ERI) Model on employee well-being. A cross-sectional survey was conducted comprising a large representative sample of 11,636 employed Dutch men and women. Logistic regression analyses were used. Controlling for job sector, demographic characteristics (including educational level) and managerial position, employees reporting high job demands (i.e. psychological and physical demands) and low job control had elevated risks of emotional exhaustion, psychosomatic and physical health complaints and job dissatisfaction (odds ratios ranged from 2.89 to 10.94). Odds ratios were generally higher in employees reporting both high (psychological and physical) efforts and low rewards (i.e. poor salary, job insecurity and low work support): they ranged from 3.23 to 15.43. Furthermore, overcommitted people had higher risks of poor well-being due to a high effort — low reward mismatch (ORs: 3.57–20.81) than their less committed counterparts (ORs: 3.01–12.71). Finally, high efforts and low occupational rewards were stronger predictors of poor well-being than low job control when both job stress models were simultaneously adjusted. In conclusion, our findings show independent cumulative effects of both the JD-C Model and the ERI Model on employee well-being and are not significantly different in men and women as well as in young and old people. In particular, high (psychological and physical) efforts and low rewards adversely affected employee well-being. Preliminary findings also indicate excess risks of poor well-being in overcommitted persons suffering from high cost — low gain conditions at work.