The book's four main characters are ecologically minded misfits—"Seldom Seen" Smith, a Jack Mormon river guide; Doc Sarvis, an odd but wealthy and wise surgeon; Bonnie Abbzug, his young Jewish feminist assistant; and a rather eccentric Green Beret Vietnam veteran, George Hayduke.

Together, although not always working as a tightly knit team, they form the titular group dedicated to the destruction of what they see as the system that pollutes and destroys their environment, the American West.

For the gang, the enemy is those who would develop the American Southwest—despoiling the land, befouling the air, and destroying nature and the sacred purity of Abbey's desert world.

[3] In his book Screw Unto Others, George Hayduke states that Edward Abbey was his mentor and mentions The Monkey Wrench Gang as the origin of the term monkey-wrenching.

Many scenes of vandalism and ecologically motivated mayhem, including a billboard burning at the beginning of the book and the use of caltrops to elude a group of vigilantes, are presented in sufficient detail as to form a skeletal how-to for would-be saboteurs.