As data rates scale, intra-pair skew has become a critical bottleneck for high-speed differential signaling. Current analytical models are often limited, while 3D electromagnetic simulations are computationally intensive. This paper presents a comprehensive analytical framework for intra-pair skew in generic asymmetric coupled transmission lines, explicitly integrating skew into S-parameter formulations. We introduce the Intra-pair Skew Propagation Graph (ISPG), a novel graph-based methodology for calculating cumulative skew in complex, cascaded channels. The proposed framework is validated against both S-parameter simulations and empirical measurements of a 2m bulk twinax cable assembly, demonstrating excellent accuracy and robustness for high-speed interconnect design.