The themes of Comanche Moon often mirror (or presage, depending on one's viewpoint) those of Lonesome Dove. We see the theme of honesty brought up with Woodrow Call, yet this time we see him with Maggie, Newt's mother. Maggie loves him, yet he cannot admit—we do not even know if he has—any affection for her. He stays with her when she is afraid, after the Indian raid on Austin; he spends time with her when she is pregnant with Newt, whom she knows is Call's son, a fact that he suspects, though unwilling to admit it. The beginning of unrequited love—between Maggie and Call, between Gus and Clara Forsythe (the married Clara Allen in Lonesome Dove)—is shown: Gus proposes to Clara the day he meets her; he is unmanned and driven to drunkenness when she announces to him that she will marry Bob Allen, a more dependable person with a much safer livelihood. The desire for a stable relationship on the part of both women indicates a gender-based difference in outlook; men consider themselves relatively free, whereas women crave solidity and security—hardly surprising in such a violent land. That the safety of the state capital is destroyed by the Indian raid on Austin rocks the foundation of the nascent society, but in the end only makes them more determined to exterminate the threat.

Another theme worth noting is that of government and organization. Both cultures seem to have their moments of anarchy and disorganization (Blue Duck ultimately kills his father, the chief). But the white society seems less organized than the Indian. Buffalo Hump's people know their place, as do Ahumado's. Austin, on the other hand, has a politically impotent governor and a town alleging civilization but, to the reader's eyes, poorly protected, dirty, and ramshackle. The Rangers are no less poorly led; Inish Scull abandons them and leaves them leaderless except for Gus and Call. Buffalo Hump, on the other hand, leads a successful raid; when he calls for warriors to follow him, hundreds answer his call.

This is of course extremely ironic, for most readers with a sense of U.S. and Western history will know that it is the white society that will eventually prevail in the world of the novel. The whites, as Buffalo Hump and other Indians suspect, will prevail because of their numbers. Seemingly, it is not a town and the trappings of civilization that make a society organized, but rather the degree to which, its citizens are cohesive and unified. The Austin society is idiosyncratic, its citizens working individually; the Indian society (with the exception of Blue Duck) seems to be of one purpose.