The theme of Arrowsmith is devotion to work as typified by Martin's absorption in pure science.
The plot of Arrowsmith, though somewhat rambling, is the best organized of all the Lewis novels. S. N. Grebstein, in Sinclair Lewis (1962), comments that the book's narrative component is superior to that of Main Street and Babbitt because the story moves beyond conflicts and centers upon the doctor's war with death. "This grappling with the universal is a rare thing in his [Lewis'] work," according to Professor Grebstein, and "Arrowsmith demonstrates more of Lewis the philosopher than any other novel."
Arrowsmith is divided into forty chapters, each subdivided into shorter sections headed by roman numerals. The book is therefore well adapted for "pick-up" reading since each short unit is complete in itself, at the same time advancing the action and illuminating the background of the novel as a whole. In structure, the book contains eight principal episodes:
- Martin's training as a physician-scientist and his marriage to Leora (Chapters I-XI)
- His experiences as a country doctor in Wheatsylvania (Chapters XII-XXVIII)
- The years in Nautilus (Chapters XIX-XXIV)
- Experience in Rouncefield Clinic (Chapter XXV)
- With McGurk Institute, in New York (Chapters XXVI-XXX)
- The West Indian adventure (Chapters XXXI-XXXV)
- Return to New York and marriage to Joyce (Chapters XXXVI-XXXIX)
- Decision to join Wickett in Vermont (Chapter XL)
Each major episode is almost a complete story in itself although linked to the whole by the growth and development of the central character. Other characters are important as their lives are intertwined with his. Suspense is maintained throughout the novel, but the ending is rather a letdown after the excitement of the fight against disease in the West Indies.