Convergence of the Indian Plate towards Eurasia has led to the building of the Himalaya, the highest mountain range on Earth. Active mountain building involves a complex interplay between permanent tectonic processes and transient seismic events, which remain poorly understood. In this Review, we examine the feedbacks between long-term tectonic deformation (over millions of years) and the seismic cycle (years to centuries) in the Himalaya. We discuss how surface morphology of the Himalaya indicates that the convergence is largely accommodated by slip on the Main Himalayan Thrust plate boundary fault, which developed in the roots of the mountain range over millions of years. At shorter (decadal) timescales, tectonic geodesy reveals that elastic strain is periodically released via earthquakes. We use examples from earthquake cycle models to suggest that partial ruptures could primarily occur in the downdip region of the Main Himalayan Thrust. Great (Mw 8+) Himalayan earthquakes are more commonly associated with complete megathrust ruptures, which release accumulated residual strain. By synthesizing numerous observations that co-vary along strike, we highlight that tectonic structures that developed over millions of years can influence stress accumulation, structural segmentation, earthquake rupture extent and location, and, consequently, the growth of the mountain range. Mountain building involves complex and debated feedback cycles between both permanent tectonic and transient seismic processes. This Review discusses how the fault architecture and tectonic segmentation of the Himalaya influence the seismic cycle, which in turn impacts the long-term growth of the mountain range.