The company traces its roots back to 1953 when Eli Lilly introduced their first antibiotic aimed at veterinary usage with the new plant and animal sciences research being combined into Lilly's Agro-Industrial division led by George Barnes. In the 1960s, the Agro-Industrial division was reorganised launching Elanco Products, short for the parent company name, Eli Lilly and Company.^[4]

In the 1980s research moved away from plant sciences and focused on animal health and food quality. In the 1990s another reorganisation led to the company being renamed Elanco Animal Health, focusing solely on animal health.^[4]

In 2007 the business acquired Ivy Animal Health and launched its companion animal business. In 2008 Elanco partnered with Heifer International. In 2009 the business launched its data analytics business, Elanco Knowledge Solutions.^[4]

In 2010 the business acquired the European rights to a portfolio of Pfizer Animal Health treatments and an Irish manufacturing site.^[5] In 2011, Elanco expanded its footprint in Europe, acquiring Janssen Animal Health.^[6] In 2012 the business acquired ChemGen Corp.^[7] In 2014, the business acquired Lohmann SE and Lohmann Animal Health for an undisclosed sum^[8] and Novartis Animal Health for $5.4 billion. In 2016 Elanco expanded its US-based business, acquiring vaccines from Boehringer Ingelheim Vetmedica for $885 million.^[9]

In 2013, Elanco made a $100M investment in China Animal Healthcare.^[10]

In 2018, Lilly announced plans to separate its Elanco Animal Health unit from the rest of the business via an initial public offering on the New York Stock Exchange, with the stock-ticker ELAN. In 2019, the divestiture was completed and Elanco launched on the New York Stock Exchange. In the same year, the US FDA approved rabacfosadine, a first-in-class treatment for canine lymphoma. The business continued to expand is US-business, acquiring Aratana Therapeutics,^[11] and its first-in-class treatment for canine osteoarthritis. Elanco also announced it would acquire the developer of vaccines for bacterial disease prevention in food-animals, Prevtec Microbia, Inc.^[12] In the same year the business announced it would acquire Bayer's animal health business for $7.6 billion.^[13][14]

On December 3, 2020, Elanco announced plans to build a new global headquarters in Indianapolis at the site of the former GM stamping plant, which is located across the White River from the downtown area. The business plans to break ground on the new headquarters in the first half of 2021.^{[15][needs update]}

In August 2021, Elanco announced it had closed its acquisition of Kindred Biosciences.^[16]

Elanco's flea and tick collar, branded "Seresto," which was developed by Bayer Animal Health and acquired by Elanco in 2020, has been linked to more than 98,000 incidents of poisoning by pesticide, including more than 2,000 pet deaths, according to a 2022 report by a subcommittee of the House Committee on Oversight and Reform. The collars are not registered for sale in Canada.^[17][18]

On July 13, 2023, following a multi-year review, the EPA announced that they were unable to determine whether Seresto was the cause for reported animal deaths. The EPA limited the collar's registration to five years instead of the normal fifteen years registration, as other pesticides normally receive. Elanco and the EPA also agreed to develop a program designed to enhance data collection for adverse event reports and continued annual enhanced reporting of Seresto adverse event data.^[19]

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