Bridgman entered Harvard University in 1900, and studied physics through to his Ph.D. From 1910 until his retirement, he taught at Harvard, becoming a full professor in 1919. In 1905, he began investigating the properties of matter under high pressure. A machinery malfunction led him to modify his pressure apparatus; the result was a new device enabling him to create pressures eventually exceeding 100,000 kgf/cm (10 GPa; 100,000 atmospheres). This was a huge improvement over previous machinery, which could achieve pressures of only 3,000 kgf/cm (0.3 GPa). This new apparatus led to an abundance of new findings, including a study of the compressibility, electric and thermal conductivity, tensile strength and viscosity of more than 100 different compounds. Bridgman is also known for his studies of electrical conduction in metals and properties of crystals. He developed the Bridgman seal and is the eponym for Bridgman's thermodynamic equations.

Bridgman married Olive Ware, of Hartford, Connecticut, in 1912. Ware's father, Edmund Asa Ware, was the founder and first President of Atlanta University. The couple had two children and were married for 50 years, living most of that time in Cambridge. The family also had a summer home in Randolph, New Hampshire, where Bridgman was known as a skilled mountain climber.

His philosophy of science book The Logic of Modern Physics (1927) advocated operationalism and coined the term operational definition. In 1938 he participated in the International Committee composed to organise the International Congresses for the Unity of Science. He was also one of the 11 signatories to the Russell–Einstein Manifesto.

Bridgman received Doctors, honoris causa from Stevens Institute (1934), Harvard (1939), Brooklyn Polytechnic (1941), Princeton (1950), Paris (1950), and Yale (1951). He received the Bingham Medal (1951) from the Society of Rheology, the Rumford Prize from the American Academy of Arts and Sciences (1919), the Elliott Cresson Medal (1932) from the Franklin Institute, the Gold Medal from Bakhuys Roozeboom Fund (founder Hendrik Willem Bakhuis Roozeboom) (1933) from the Royal Netherlands Academy of Arts and Sciences, and the Comstock Prize (1933) of the National Academy of Sciences.

Bridgman was a member of the American Physical Society and was its President in 1942. He was also a member of the American Association for the Advancement of Science, the American Academy of Arts and Sciences, the American Philosophical Society, and the National Academy of Sciences. He was a Foreign Member of the Royal Society and Honorary Fellow of the Physical Society of London.

The Percy W. Bridgman House, in Massachusetts, is a U.S. National Historic Landmark designated in 1975.

In 2014, the Commission on New Minerals, Nomenclature and Classification (CNMNC) of the International Mineralogical Association (IMA) approved the name bridgmanite for perovskite-structured (Mg,Fe)SiO₃, the Earth's most abundant mineral, in honor of his high-pressure research.