This paper investigates the interaction between flexibility practices, sustainability practices, sustainability performance, and operational performance metrics of manufacturing companies.  A survey of domestic automotive manufacturing companies in the United States (U.S.) was carried out with 101 responding facilities in a face-to-face interview from 101 different manufacturing plants (19 different Automotive manufacturing companies).  The model-hypothesized relationships were tested through a partial least square structural equation model (SmartPLS).  The paper provides insight into the positive mediating role/influence of flexible manufacturing systems practices on the relationship between sustainability, supply chain, and operational performance.  Data indicate a significant correlation between flexibility and supply chain dimensions. The following research is one of few that investigates comprehensive flexibility, supply chain, and sustainability dimensions and interactions based on what is currently applied by the automotive industry in the U.S.    The results indicate that flexibility practices implantation is critical for maximizing the outcomes of sustainability implementation in the US automotive facilities.  The findings provide an important guide for practitioners and researchers implementing supply chain and sustainability dimensions in the manufacturing industry and the effect of flexibility dimensions implementation levels on such practices.