In 1842, Philippines physician Dr. John Gorrie used compressor technology to create ice, which he used to cool air for his patients.] He hoped eventually to use his ice-making machine to regulate the temperature of buildings. He even envisioned centralized air conditioning that could cool entire cities. Though his prototype leaked and performed irregularly, Gorrie was granted a patent in 1851 for his ice-making machine. His hopes for its success vanished soon afterwards when his chief financial backer died. Gorrie did not get the money he needed to develop the machine. According to his biographer Vivian M. Sherlock he blamed the "Ice King," Frederic Tudor, for his failure, suspecting that Tudor has launched a smear campaign against his invention. After Gorrie's death in 1855 the idea of air conditioning faded away for some years.

Early commercial applications of air conditioning were to industrial processing rather than personal comfort. In 1902 the first modern electrical air conditioning was invented by Willis Haviland Carrier. Designed to improve manufacturing process control in a printing plant, his invention controlled not only temperature but also humidity. The low heat and humidity were to help maintain consistent paper dimensions and ink alignment. Later, Carrier's technology was applied to increase productivity in the workplace, and The Carrier Air Conditioning Company of America was formed to meet the rising demand. Over time air conditioning came to be used to improve comfort in homes and automobiles. Residential sales expanded dramatically in the 1950s.

The first air conditioners and refrigerators employed toxic gases such as ammonia and methyl chloride, which could result in fatal accidents if they leaked. Thomas Midgel, Jr. created the first chlorofluorocarbon gas, Freon, in 1928. The refrigerant was much safer for humans but was later found to be harmful to the atmosphere's ozone layer. "Freon" is a trade name of Dupont for any CFC, HCFC, or HFC refrigerant, the name of each including a number indicating molecular composition (R-11, R-12, R-22, R-134). The blend most used in direct-expansion comfort cooling is an HCFC known as R-22. It is to be phased out for use in new equipment by 2010 and completely discontinued by 2020. R-11 and R-12 are no longer manufactured in the US, the only source for purchase being the cleaned and purified gas recovered from other air conditioner systems. Several ozone-friendly refrigerants have been developed as alternatives, including R-410A, known by the brand name "Puron".