Dr. Martin Arrowsmith aspires to become a medical research scientist. When he impulsively marries nurse Leora Tozer, he instead decides to open a country medical practice in South Dakota to support his wife better than he could as a laboratory assistant. After a few years of working in his medical practice, Arrowsmith believes that his intuitions are not that well-suited to the job as compared to research. He takes up the offer of Dr. Max Gottlieb, his professor and mentor at Winnemac College, for a research position at the McGurk Institute in New York City. After years of research, Arrowsmith stumbles across a discovery, its practical uses he is initially unsure. When a case of bubonic plague hits an island in the West Indies, respected Swedish scientist Dr. Gustav Sondelius believes that Arrowsmith's discovery could be used as a serum to kill the plague. Despite the personal risk, Arrowsmith travels to the West Indies to see if the serum does indeed work. The serum being untested, Arrowsmith must make the difficult decisions between short term human sacrifices versus the long term benefit to mankind, and between the goals of the institute versus his own ideals. Through it all, Arrowsmith tries to protect Leora from the dangers he faces, she who stands steadfastly by her husband.