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Purpose There has been a growing emphasis in both academic and industry spheres on the importance of efficient supply chain management. However, supply chains are facing unprecedented levels of upheaval and unforeseen events. From natural disasters to artificial crises, political and economic turmoil and the ever-changing landscape, uncertainties abound. Therefore, this study investigates the effects of structural risk sharing, structural collaboration, supply chain ambidexterity, dynamic reconfiguration, dynamic sensing and supply chain flexibility on supply chain resilience. Design/methodology/approach Data were collected from 2,301 manufacturers across various industries in the USA. The hypotheses were evaluated using Structural Equation Modeling through Smart PLS version 4.0. Findings All direct and sequential mediation hypotheses were supported. Structural collaboration exerted a stronger effect on supply chain ambidexterity than structural risk sharing. Supply chain ambidexterity strongly enhanced dynamic sensing and reconfiguration, thereby improving supply chain flexibility. Notably, supply chain flexibility emerged as the strongest direct predictor of resilience. The most influential indirect pathway was structural collaboration → ambidexterity → dynamic sensing → flexibility → resilience, underscoring flexibility as the primary mechanism through which structural practices translate into resilience outcomes. Originality/value Sequential mediation introduces innovation by highlighting the impact of supply chain ambidexterity, which benefits both the firm and the broader supply chain network. Prior investigations concentrated on the internal implications of supply chain ambidexterity within a firm. Nonetheless, informed by the dynamic capability view, the variables studied indicate that supply chain ambidexterity empowers firms to navigate intricate supply chain challenges and capitalize on opportunities. This implies that firms can adapt to evolving market conditions, harmonize their operations with their objectives and enhance the resilience of their supply chains against disruptions.