comely
Explanation
The Joke
The comic depicts Jesus returning to Heaven after his time on Earth and stumbling upon Isaiah 53:2 in the Bible. The verse reads: "He hath no form nor comeliness; there is no beauty that we should desire him." Jesus is outraged by this unflattering biblical description of himself, shouting "Screw you, humanity! How does two thousand years of strife sound?!" -- implying that humanity's long history of religious conflict is essentially divine payback for the Bible calling Jesus unattractive.
The caption at the bottom clarifies the scenario: "Shortly after returning to Heaven, Jesus stumbles upon Isaiah 53:2." This frames the entire strip as an origin story for centuries of human suffering, all stemming from a petty act of vanity.
The Humor
The comedy works on multiple levels. First, there is the absurdity of reducing millennia of religious wars, persecution, and suffering to a case of hurt feelings about one's physical appearance. Second, it plays on the very human trait of vanity -- even the Son of God is not above being insulted by an unflattering description. The joke subverts the theological reading of Isaiah 53:2 (traditionally interpreted as a prophecy about the Messiah's humble appearance) by treating it as a personal insult that Jesus takes very, very badly. SMBC frequently mines humor from imagining divine or cosmic beings reacting to situations with petty, all-too-human emotions.
References
Isaiah 53:2 is a real verse from the Hebrew Bible/Old Testament, part of the "Suffering Servant" passage. Christian theology traditionally interprets this chapter as a messianic prophecy about Jesus Christ, describing how the Messiah would be unremarkable in appearance and rejected by people.