South Africa faces significant challenges in fostering sustainable economic growth through effective collaboration between large firms and small to medium-sized enterprises (SMEs). The comparative analysis employs a mixed-method approach, integrating qualitative interviews with quantitative surveys among selected large firms and SMEs across various sectors in South Africa. A notable finding is that successful business linkages often involve tailored partnership agreements rather than generic collaborations, which significantly enhance mutual benefits and growth prospects. The study underscores the importance of strategic planning, trust-building mechanisms, and mutual value creation as foundational elements for fostering robust business relationships between large firms and SMEs in South Africa. Policy-makers should promote sector-specific matchmaking events to facilitate more targeted partnerships. Businesses are encouraged to develop clear communication channels and shared performance metrics. South Africa, Business Linkages, Large Firms, Small to Medium Enterprises (SMEs), Collaboration Strategies