<p>In current resilience-based earthquake engineering methodologies, the functionality loss of building components is predominantly assessed through macroscopic engineering demand parameters (EDPs). However, adopting these EDPs to evaluate spatially distributed component damage in irregular buildings results in inaccuracies. Furthermore, existing frameworks lack a comprehensive understanding of cascading failures within building functional systems caused by interdependencies among components. This paper proposes a framework for analyzing the spatiotemporal evolution of seismic functionality loss in irregular buildings. First, a computational model for assessing the time-variant functionality loss of structural components is developed by employing a weighted volume average of damage variables. Next, a time-variant functionality loss computational model for nonstructural components is established using local structural dynamic responses, with region partitioning and a matrix algorithm as the computational foundation. Furthermore, to address the functionality cascading failure characteristics inherent in subsystems and components of irregular buildings, the fault tree approach is integrated, enabling spatiotemporal simulation of functionality loss propagation. A case study demonstrates the ability of the proposed framework to identify system functionality weak links, evaluate seismic performance, conduct building vulnerability analyses, and provide insights into the actual functional failure mechanisms of irregular buildings.</p>