Solomon, working with colleagues at the NOAA Earth System Research Laboratories, postulated the mechanism that the Antarctic ozone hole was created by a heterogeneous reaction of ozone and chlorofluorocarbons free radicals on the surface of ice particles in the high altitude clouds that form over Antarctica. In 1986 and 1987 Solomon led the National Ozone Expedition to McMurdo Sound, where the team gathered the evidence to confirm the accelerated reactions. Solomon was the solo leader of the expedition, and the only woman on the team. Her team measured levels of chlorine oxide 100 times higher than expected in the atmosphere, which had been released by the decomposition of chlorofluorocarbons by ultraviolet radiation.
Solomon later showed that volcanoes could accelerate the reactions caused by chlorofluorocarbons, and so increase the damage to the ozone layer. Her work formed the basis of the U.N. Montreal Protocol, an international agreement to protect the ozone layer by regulating damaging chemicals. Solomon has also presented some research which suggests that implementation of the Montreal Protocols is having a positive effect.
Using research work conducted by English explorer and navy officer Robert Falcon Scott, Solomon also wrote and spoke about Scotts 1911 expedition in The Coldest March: Scotts Fatal Antarctic Expedition to counter a longstanding argument that blamed Scott for his and his crew's demise during that expedition. Scott attributed his death to unforeseen weather conditions – a claim that has been contested by British journalist and author Roland Huntford. Huntford claimed that Scott was a prideful and under-prepared leader. Solomon has defended  Scott and said that "modern data side squarely with Scott", describing the weather conditions in 1911 as unusual.
For her critical contribution to saving the ozone layer, Solomon was a winner of the 2021 Future of Life Award along with Joe Farman and Stephen O. Andersen. Dr. Jim Hansen, former Director of the NASA Goddard Institute for Space Studies and Director of Columbia Universitys Program on Climate Science, Awareness and Solutions said, "In Farman, Solomon and Andersen we see the tremendous impact individuals can have not only on the course of human history, but on the course of our planets history. My hope is that others like them will emerge in today's battle against climate change." Professor Guus Velders, a climate scientist at Utrecht University said, "Susan Solomon is a deserving recipient of the Future of Life Award. Susan not only explained the processes behind the formation of the ozone hole, she also played an active role as an interface between the science and policy of the Montreal Protocol."