I really think Randall lost his wife.
Web cartoonists often put their life into their work, and in the early days we saw stick figures having sex a lot. Later, there was the cancer arc, where the fiancee/wife gets cancer with the last mention being
in 2020. Most couples eventually have a baby (if they went with the white liberal route of a beloved pet as baby surrogate, I would expect to see more cat/dog comics). I've thought with the curious absence of real life, whether a kid, pet, or beloved wife, was odd.
So there are a few theories I have that could've happened:
1) With no stable ground of why they married beyond "I like having sex with you", they got divorced. This could be anything. Either "Megan" (ExplainXKCD's name for the female character) wanted a kid and Randall wasn't having it, or something else happened that drove a wedge in their relationship and they separated.
2) She's been dead for a while. Randall's further descent into leftist politics is cope.