Arrowsmith by Sinclair Lewis is the story of Martin Arrowsmith, who is born and raised in the small Midwestern town of Elk Mills. Martin has a keen interest in science and spends all his free time studying and reading through medical journals and other books at Doc Vickerson, the town Doc's office (this is very similar to Sinclair Lewis's own early life and introduction to reading).

This early interest in science and medicine is supplemented when Arrowsmith goes to college and becomes a medical student at the University of Winnemac, where he meets his life-time mentor, Max Gottlieb, a German Professor.

While in medical school, Martin falls in love with Leora Tozer, a down-to-earth nurse in training, whom he marries and loves with all his heart until her tragic death. While at Winnemac, under the wing of Gottlieb, Martin develops a deep-rooted love research in its truest form.

He hates how his research is used, however, and lashes out against "commercialism" of most medical research. In spite of his feelings Martin must abandon his preference for pure research due to his need to support his wife.

Martin and Leora move to her hometown of Wheatsylvania where Martin becomes a country doctor whom the townspeople love to gossip about. Although he is at times successful, he never gains the trust of the community as a whole after losing a patient in the early days of his practice. Feeling as though they have failed in Wheatsylvania, Martina and Leora move to Nautilus, a city in the Midwest.

In Nautilus, Martin becomes a public health physician working under Dr. Pickerbaugh, who is more of a salesman than a doctor. Unhappy in Nautilus, Martin is hired to work at the Rouncefield Clinic in Chicago to work with his former medical school colleague, Angus Duer. His work as a pathologist in the Rouncefield Clinic, however, also proves disheartening given that the Clinic is a playground for doctors who care more for money than anything else.

It is at this point that Martin gains the attention of Max Gottlieb. Gottlieb, who is working at the prestigious McGurk Research Institute in New York (modeled after the Rockefeller Institute in New York), invites Martin to join his research team. Martin is glad to be able to finally have his chance to practice laboratory science, the "true science" he has been forced to abandon more than once in his career.

Martin Arrowsmith is happy there until he begins to be rushed in his study and work. The heads of the Institute begin to pry into his research pushing Martin to publish and "sell" his work or seek to work elsewhere. While at the institute, however, Martin comes across a huge breakthrough that is a triumph in his career and research. His breakthrough was the isolation of a special anti-bacterial strain that seems to kill pneumonia and plague.

Although there is some disappointment when finding out much of his research had already been discovered and published, Martin decides to further his research and is successful in his additional work. Arrowsmith is sent to test his discovery in the Caribbean island of St. Hubert, which has become devastated by the plague. Martin agrees to conduct his experimental research on the quarantined island of St. Hubert and his wife Leora accompanies him.

On the island of St. Hubert, Martin does, in fact, seem to cure the people of the plague. However, the research conducted on the island is not altogether precise because Martin had given up on his work for a time, after the tragedy of his wife's (Leora) death due to the plague he was sent there to cure, certainly a bitterly ironic turn of events. Martin goes through a period of mourning in which he abandons his research.

It is also on the island that Martin meets Joyce Lanyon, an immensely wealthy woman whom he marries when he returns to New York. Martin cannot grow used to his new wife's wealthy lifestyle and finds himself, once again, unhappy. He leaves her and the child they had together and retreats into the wilderness with Terry Wickett, his friend and colleague from the McGurk Institute.

Spoiler Alert!!

The book finishes with Martin and Terry's planning to build a research lab in Terry's home in the woods so that they may be left to do the important research they feel compelled to complete without the politics and pressure placed upon researchers by educational department heads and the presidents of institutes who must show profitability to gain grants and other funding.