The first Lysol Disinfectant spray was introduced in 1889 by Gustav Raupenstrauch to help end a cholera epidemic in Germany. The original formulation of Lysol contained cresols. This formulation may still be available commercially in some parts of the world. Formulations containing chlorophenol are still available in the United Kingdom.

• 1930: Lysol Brand Disinfectant Liquid was introduced to drug stores and hospitals.
• 1957/58 Lysol purchased the rights to private label National Laboratories, Inc's Disinfectant spray.
• 1962: Lysol released the Lysol Disinfectant Spray, which used a new method of aerosol application.
• 1968: Lysol began creating bathroom cleaners and released the Lysol Toilet Bowl Cleaner.
• 1985: Lysol All Purpose Cleaner was released.
• 1988: Lysol began shipping aerosol disinfectants to humid areas such as Houston, to combat occupational lung diseases, (also known as "lung rot").
• 2000: Pre-moistened Lysol Brand Disinfecting Wipes was released, a cleaning wipe for use on hard, non-porous surfaces.
• 2009: Lysol began producing hand soaps.

In March 2020, the Lysol brand made a $2 million contribution to a fund dedicated to the COVID-19 campaign in partnership with the US State Center for Disease Control and Prevention (CDC).

In July 2020, the US Environmental Protection Agency (EPA) approved two Lysol products as effective agents against SARS-CoV-2 when used on hard surfaces.