Objective: Large-scale infrastructure is characterized by vast scale, technical complexity, multiple stakeholders, and high risk. Enhancing the efficiency of program management in the context of large-scale infrastructure is crucial for economic and social development in China. Owners are important in the construction of large-scale infrastructure. However, the existing research lacks a comprehensive understanding of key factors involved in program management from owners' perspective and has not systematically explored the underlying mechanisms. This study aims to establish a management capability index system, particularly for program management in the context of large-scale infrastructure from the owners' perspective, and construct and validate a theoretical model for such management activities. Methods: This study adopted a hybrid approach combining field investigations, surveys, and case studies, focusing on the Shenzhen Bay Super Headquarters Base—a large-scale infrastructure program encompassing 17 projects. During field investigations, qualitative data were gathered based on stakeholders' management needs and challenges associated with large-scale infrastructure program management. Based on an extensive literature review, a questionnaire was designed and distributed to the management and technical personnel operating within the program. This survey generated 407 valid responses, thus providing a robust dataset. The quantitative analysis undertaken employed word frequency and social network analysis to identify primary management demands. Sample mean estimation was employed to gain insights into the current state of program management. Hierarchical cluster analysis was subsequently employed to delineate key owner capabilities critical to effective program management. The proposed theoretical model was tested via partial least squares structural equation modeling (PLS-SEM) to validate the relationships among owners' program-management capabilities, external program conditions, partnership, resource allocation, and program performance. The reliability and validity of the model were rigorously tested, and the model's path coefficients, explanatory power, and predictive power were also assessed. Results: Textual analysis results identified a pressing requirement for owners to coordinate the design, procurement, and construction stages of projects to optimize the overall effectiveness of program management. Hierarchy cluster analysis results revealed three key program-management capabilities of owners: construction management, dynamic, and information technology capabilities. The PLS-SEM analysis results validated the proposed model, highlighting the notable positive effects of the owners' program-management capabilities and external program conditions on program performance. Specifically, two important paths were identified: (1) owners' program-management capabilities → partnership → (resource allocation) → program performance and (2) external program conditions → partnership→ (resource allocation) → program performance. Conclusions: The findings of this study offer theoretical insights and practical guidance for enhancing program management in the context of large-scale infrastructure. The findings confirm that the owners are critical stakeholders in managing large-scale infrastructure programs. Comprehensive owners' program-management capabilities can considerably enhance program performance by cultivating partnerships between stakeholders and improving resource allocation. Further, this study highlights the important influence of external program conditions on program outcomes, emphasizing the need for owners to adapt to dynamic external environments. Moreover, practical recommendations are provided for managing large-scale infrastructure programs from owners' perspective, suggesting that owners should systematically identify and address constraints within the program's lifecycle, enhance their dynamic capabilities to effectively adapt to complex external conditions, foster collaborative relationships with diverse stakeholders, and facilitate the integration of advanced information technologies within program management.