Beyond the Hundredth Meridian, by Wallace Stegner, is a work of non-fiction concentrating on the expeditions, government career and scientific work of Major John Wesley Powell. The book begins in 1868 and continues until Powell's death in 1902.

Powell was raised in Midwest America in the years leading to and including the Civil War. When the country began to turn its eyes towards the expansion of the country to the West, Powell was intrigued by the possibilities of scientific expeditions and exploration. He established himself with an Illinois educational institution and began minor, then major expeditions. Gathering qualified personnel and collaborators, somewhat meager financial support and applying his personal determination, Powell launches the first successful expedition to follow the Colorado River through the Grand Canyon.

Powell becomes fascinated with many aspects of science. He develops many theories, and devises projects and expeditions to find facts that will support or repute his theories. After the expedition, Powell enters government service, first in the Bureau of Ethnology, then with the US Geological Survey. Never one to allow mere titles to stand in the way of his interest in a field, Powell continues to work on projects that will affect many fields of science. Powell consistently maps out the path of a project or endeavor, then finds the perfect person to carry the work to its logical conclusion.

Powell moves through the the scientific bureaus of government, organizing them, setting out goals, providing measurable projects and purpose. He leaves a legacy of management that is copied today in every level of government. Some of his projects are continuing to modern times, and many of his principles, such as the value of topographical maps, have been validated many times over.

Powell's first years with Congress and working through government channels are amazingly successful, and he is able to begin many of his projects; however, as he gains power, he gains enemies. His radical ideas about irrigation and the division of powers over land use are fought by politicians, and after a time, he returns to his old love of ethnology to finish out his career. After retirement, Powell continues working on the Sciences of Man, contributing substantially to the knowledge of the field.

As Powell and his staff members sort through the notes, mapping, surveys and data compiled by his own expeditions and those of Hayden, King and other explorers, it becomes clear to Powell that someone needs to devise a definitive plan for the expansion of the West. The plan needs to include the possibilities for mining, farming, ranching and settlement, and provide an ideal situation for the average American who is looking to homestead in the West. Powell realizes over time that the task is one he is ideally suited for and he begins his life's work.

Powell enters government work as an amateur, but as with his amateur status as a scientist, time and experience turn him into an expert. Powell gathers support from politicians, outside sources, associated institutions such as the Smithsonian, and builds a strong team for his staff.