In 1927, Pedersen began working for DuPont where he would remain for the next 42 years, retiring at the age of 65. At DuPont, his work resulted in 25 papers and 65 patents. In 1967 he published two works that are now considered classics; they describe the methods of synthesizing crown ethers (cyclic polyethers). The donut-shaped molecules were the first in a series of extraordinary compounds that form stable structures with alkali metalions. In 1987 he shared the Nobel Prize in Chemistry with Donald Cram and Jean-Marie Lehn for his work in this area; Cram and Lehn expanded upon his original discoveries.
Pedersen was diagnosed with myeloma in 1983, and though he was becoming increasingly frail, he traveled to Stockholm to accept the Nobel Prize in late 1987. Shortly thereafter, he was awarded a medal for excellence by the du Pont Research Fellows. He died on 26 October 1989 in Salem, New Jersey.