PTFE was accidentally discovered in 1938 by Roy Plunkett while he was working in New Jersey for DuPont. As Plunkett attempted to make a new chlorofluorocarbon refrigerant, the tetrafluoroethylene gas in its pressure bottle stopped flowing before the bottle's weight had dropped to the point signaling "empty." Since Plunkett was measuring the amount of gas used by weighing the bottle, he became curious as to the source of the weight, and finally resorted to sawing the bottle apart. He found the bottle's interior coated with a waxy white material that was oddly slippery. Analysis showed that it was polymerized perfluoroethylene, with the iron from the inside of the container having acted as a catalyst at high pressure. Kinetic Chemicals patented the new fluorinated plastic (analogous to the already known polyethylene) in 1941,and registered the Teflon trademark in 1945.

By 1948, DuPont, which founded Kinetic Chemicals in partnership with General Motors, was producing over two million pounds (900 tons) of Teflon brand PTFE per year in Parkersburg, West Virginia.An early use was in the Manhattan Project as a material to coat valves and seals in the pipes holding highly reactive uranium hexafluoride at the vast K-25 uranium enrichment plant in Oak Ridge, Tennessee.[8]

In 1954, the wife of French engineer Marc Grégoire urged him to try the material he had been using on fishing tackle on her cooking pans. He subsequently created the first Teflon-coated, non-stick pans under the brandname Tefal (combining "Tef" from "Teflon" and "al" from aluminum).In the United States, Marion A. Trozzolo, who had been using the substance on scientific utensils, marketed the first US-made Teflon-coated pan, "The Happy Pan", in 1961.

However, Tefal was not the only company to utilize PTFE in nonstick cookware coatings. In subsequent years, many cookware manufacturers developed proprietary PTFE-based formulas, including Swiss Diamond International, which uses a diamond-reinforced PTFE formula;Scanpan, which uses a titanium-reinforced PTFE formula;and both All-Clad and Newell Rubbermaid's Calphalon, which use a non-reinforced PTFE-based nonstick.[14] Other cookware companies, such as Meyer Corporation's Anolon, use Teflon nonstick coatings purchased from DuPont.

In the 1990s, it was found that PTFE could be radiation cross-linked above its melting point in an oxygen-free environment.Electron beam processing is one example of radiation processing. Cross-linked PTFE has improved high-temperature mechanical properties and radiation stability. This was significant because, for many years, irradiation at ambient conditions had been used to break down PTFE for recycling.The radiation-induced chain scission allows it to be more easily reground and reused.