The novel follows two boys who both go by the name Will Grayson. The first Will, whose name is always correctly capitalized, is described as trying to live his life without being noticed. This is complicated by the fact that his best friend, Tiny Cooper, described as "the world's largest person who is really, really gay" and "the world's gayest person who is really, really large", is not the type to go around unnoticed. Tiny is also, throughout the novel, trying to create an autobiographical musical, which further draws attention to himself and everyone around him. The other will grayson, whose name is never capitalized, goes through his life without anything good to hold onto besides an online friendship with someone who goes by the name Isaac. Intent on meeting up with Isaac, will grayson sets up an encounter one night in Chicago but eventually finds out that Isaac was invented up by Maura. What ensues brings both characters together and changes both of their lives forever in ways they could never have guessed or imagined.