Environmental historian J. R. McNeill opined that Midgley "had more impact on the atmosphere than any other single organism in Earth's history", and Bill Bryson remarked that Midgley possessed "an instinct for the regrettable that was almost uncanny". The New Scientist called him a "one-man environmental disaster".

The team eventually synthesized dichlorodifluoromethane, the first chlorofluorocarbon (CFC), which they named "Freon".

On October 30, 1924, Midgley participated in a press conference to demonstrate the apparent safety of TEL, in which he poured TEL over his hands, placed a bottle of the chemical under his nose, and inhaled its vapor for 60 seconds, declaring that he could do this every day without succumbing to any problems.

In 1923, Midgley took a long vacation in Miami, Florida, to cure himself of lead poisoning. He found "that my lungs have been affected and that it is necessary to drop all work and get a large supply of fresh air".

Midgley discovered that the addition of tetraethyllead (TEL) to gasoline prevented "knocking" in internal combustion engines. The company named the substance "Ethyl", avoiding all mention of lead in reports and advertising.

An octane rating, or octane number, is a standard measure of a fuel's ability to withstand compression in an internal combustion engine without detonating. The higher the octane number, the more compression the fuel can withstand before detonating.