Blasting at the Big Ugly is a first-person, non-linear novel with two major thru-lines. The first is the story of narrator Ethan and his comrades Jake and Brett as they run around an active mountaintop removal coal mine in West Virginia shooting off flares and evading capture to prolong mining and to cost the coal company profits.

The second thru-line details Ethan's inheritance of family land at Big Ugly Creek from his grandfather and how meeting his eventual love interest Kate at a protest in Washington, DC, leads him to move to the land, where his great aunt Patsy still lives. Through Kate, Ethan gets involved with the anti-MTR movement in the coalfields but becomes increasingly frustrated by the lack of progress. On a five day march, Ethan meets Jake, a veteran of the War in Iraq who encourages Ethan to radicalize his protest. His friendship with the unpredictable and sometimes violent Jake, along with an episode of infidelity while she visits her sick father in Wisconsin, erodes and eventually ends Ethan and Kate's relationship.

The mousing operation quickly goes awry when Brett is captured by guards and arrested. Ethan and Jake continue for days until Ethan falls and fractures his rib. Instead of continuing with their action, Ethan surrenders himself to a miner to seek medical attention. Jake does not surrender, and in a struggle shoots a miner with a flare gun to the chest, steals and crashes a miner's truck. Ethan is hospitalized for frostbite, a concussion, and a fractured rib, charged with trespassing and reckless endangerment, and let out on bail. Once back home, a snowstorm locks Ethan, Kate, Patsy, and Ethan's father at Big Ugly. A few weeks later, after Jake has been arrested for the shooting of the miner, Ethan learns that Jake has committed suicide in prison.

The book ends after Ethan has already left Big Ugly, on a drive to visit Jake's family.