Title text: Some people haven't heard of the Donner Party. They were pioneers who got stranded and likely resorted to cannibalism.
In the early days of xkcd (and days when Wikipedia was not quite in the mainstream consciousness), Randall didn't trust people to understand his comics or his references, and often explained the joke in the title text.
As the title-text says, the Donner party was a group of pioneers who set out west along a new route that was supposed to be easier to travel, but ultimately proved slow and treacherous. They became trapped in the Sierra Nevada mountains and many died.
Low on food, it is believed that many of the pioneers resorted to cannibalism, eating the bodies of party members who had already died. In this one-frame comic, Donner party members arrive at Joe's (a restaurant, apparently) only to decide that they are full. The fact that the maitre d’ calls for a party of four and only three people are present suggests that they have eaten the fourth member of their party. Of course they are not in a survival situation in this strip, making cannibalism completely unnecessary.
- This is the twenty-ninth comic originally posted to livejournal. The previous was 27: Meat Cereals. The next was 34: Flowers
- [Three people stand in the foyer of a restaurant. A sign above the entryway reads "JOE'S" and there is a menu next to it. In front of the entryway, there's a host behind a podium. A sign on the podium reads "EAT IN".]
- Host: Donner, party of four?
- Man: Actually, never mind.
- Woman: We're full.