E major was a key Beethoven repeatedly turned to when he wanted to express religious and universal spirituality. This paper explores Beethoven’s musical depiction of spirituality in those pieces. My study of these works reveals three observations. First, in instrumental works, Beethoven uses the "chorale" as a musical topic to cue the listener that something spiritual is being communicated. Second, a prominent feature of the hymn topic for Beethoven and, as I will show, composers before and after him, is progression I–V–vi, especially when used at the beginning of a phrase. I discuss two possible sources, both of which make prominent use of the I–V–vi progression, that may have had some influence in the development of the hymn topic in instrumental music: protestant chorales and "priestly processionals" in 18th-century opera. The third observation is that a significant number of these works involve key relationships drawn from the major-third cycle A-flat-C-E. Beethoven was one of the earliest composers to make prominent use of major-third relations and, interestingly, he preferred the A-flat–C–E cycle over the other three possible cycles (D-flat–F–A, D–F-sharp–Bb, and E-flat–G–B). I conclude the paper with an analysis of the second movement of Beethoven’s late string quartet in E-flat major, Op. 127.