He led Mallinckrodt through the Great Depression, choosing to incur greater financial losses rather than lay off a single worker. In the absence of more productive jobs, employees were kept busy fixing equipment, painting fences and cleaning yards. He also helped his company through the war years.

Over time, he expanded the company from a small chemical producer to a major producer of fine chemicals for industry and medicine.

As a scientist, Mallinckrodt was responsible for important developments in the fields of anesthesia, atomic research and the purification and conversion of ores. His original research improved the quality and stability of ether and contributed substantially to safer surgical operations. He held 16 patents relating to the purification, packaging and preservation of the anesthetic. He also supported research at Harvard and Washington University medical schools, where chairs in anesthesiology were established by him.

Mallinckrodt donated vast sums to local universities and hospitals for education, medical research and treatment. The Mallinckrodt Institute of Radiology at Washington University School of Medicine was substantially endowed by Mallinckrodt as a tribute to his father. His philanthropies were carried out almost anonymously for many years. In 1962, he received the St. Louis Humanities Award from the St. Louis Globe-Democrat for his contributions to the community.