Plath worked as a professor of biology and German language at Boston University and as an entomologist, with a specific expertise on bumblebees.

[1] Recognizing that the demand for blacksmiths in Germany was decreasing due to increased industrialization, he sailed to the United States in September 1900, when he was 15 years old, aboard the Auguste Victoria.

He decided to stay in New York City for a while instead of following his original plan to go immediately to his grandparents' house in Fall Creek, Wisconsin.

[2] Within weeks, Plath became disillusioned with the teachings of the Wisconsin Evangelical Lutheran Synod, and dropped out of the seminary despite threats from his grandfather warning him of serious consequences if he did so.

[2] In response, John Plath ceremoniously crossed out Otto's name from the Family Bible with a pencil and disowned his grandson.

[2] After the United States declared war on Imperial Germany in May 1917, Plath was investigated on suspicion of disloyalty and refusing to buy war bonds by the Federal Bureau of Investigation, but he was found to be loyal, but not uncritical, toward his adopted country.

[4] Plath's doctoral dissertation was titled Bumblebees: Their Life History, Habits, and Economic Importance, with a Detailed Account of the New England Species.

[4] In 1929, he met Aurelia Schober while she was working on her master's degree in English and German,[3] and in 1930, he asked her to go with him to an end-of-year party at his colleague's country home.

[5] In 1935, shortly after the birth of his son Warren, Plath began to become ill.[5] After inaccurately self-diagnosing his illness as lung cancer, he refused to seek medical care.

[7] After the FBI declassified the files on its World War I investigation into the alleged disloyalty of Otto Plath, scholar Heather Clark criticized claims by Sylvia that her father had been a Nazi sympathizer.