Immediately after graduating from medical school, he became a ship's doctor in the U.S. Navy, serving during the ongoing Mexican–American War.

[2] As a Navy physician, Squibb became disenchanted with the poor quality of medicines used on American military vessels and, as a result, in 1854 he invented an improved method of distilling ether, an anesthetic.

Squibb was known as a vigorous advocate of quality control and high purity standards within the fledgling pharmaceutical industry of his time, at one point self-publishing an alternative to the U.S. Pharmacopeia (Squibb's Ephemeris of Materia Medica) after failing to convince the American Medical Association to incorporate higher purity standards.

[4][5][6][7][8][9] Squibb Corporation served as a major supplier of medical goods to the Union Army during the American Civil War, providing portable medical kits containing morphine, surgical anesthetics, and quinine for the treatment of malaria (which was endemic to the eastern United States at that time).

[1] Together, they were the parents of:[12] Squibb died on October 25, 1900, at his home, 152 Columbia Heights in Brooklyn, New York, from a ruptured blood vessel.