Hydrogen, as a clean and promising energy carrier, is considered a viable alternative fuel for the future. However, accidental hydrogen leakages and explosions pose considerable safety concerns in hydrogen energy applications and process industries. This study investigated the flame propagation characteristics of non-uniform premixed hydrogen-air mixtures in a rectangular closed duct with a length-to-diameter ratio of 5.78, taking into account varying equivalence ratios and diffusion times. First, numerical simulations using FLUENT were conducted to model the hydrogen diffusion process in a confined space, determining the hydrogen concentration evolution post-leakage. After approximately 200 s of diffusion, the premixed hydrogen-air mixtures remained in a state of homogeneous mixing, with the hydrogen concentration stabilizing at approximately 1.25 × 10−2 kg/m³. Subsequently, experimental observations were performed using a visual pipeline system, high-speed photography, and flame structure analysis. These experiments examined inhomogeneous hydrogen-air mixtures under seven different equivalence ratios and five different diffusion time conditions. The effects of equivalence ratios and diffusion times on flame propagation characteristics were analyzed. The results revealed that equivalence ratio significantly influenced the flame structure, with higher equivalence ratios producing more pronounced flame surface wrinkles. However, the typical evolution of the tulip flame remained consistent. At a constant equivalence ratio, flame propagation velocity exhibited an initial increase followed by a decrease over time. These findings demonstrate that turbulence intensity accelerated the flame propagation in non-uniform premixed hydrogen-air mixtures. This study underscores the importance of further research on hydrogen safety fundamentals and technologies to develop comprehensive safety standards.