An epigraph identifies the ironweed as a member of the sunflower family so named for its particularly rigid stem. The novel then opens with vagrant protagonist Francis Phelan riding in the back of a truck through a cemetery on Halloween, 1938, in Albany, New York, where his parents (who seem to look on as he approaches) are buried. His friend Rudy, a dimwitted tramp, is with him. As the two of them shovel dirt onto recently placed graves, they joke around and wonder about the people who are buried in the (as yet) unmarked graves.

The narrative goes back two days, showing how Francis ended up at the cemetery. A heavy drinker, Francis stops drinking when he runs out of money, at which time he goes to court for registering to vote 21 times, though the case is eventually thrown out. Unable to pay his lawyer’s modest fee, Francis agrees to work in the cemetery the following day. He then spends the night under a bridge before going to a Methodist mission that provides food and shelter to the needy, looking for his girlfriend, Helen. There, he runs into Rudy, who reveals that he has been diagnosed with stomach cancer.