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Centene was founded by Elizabeth Brinn as Managed Health Services in Milwaukee, Wisconsin, in 1984. After the death of Brinn, the non-profit organization was sold to investors. The proceeds went to the Betty Brinn Foundation, which became a major shareholder in Centene. In 1996, Michael Neidorff joined the company as chief executive.
Centene went public in December 2001. In 2006, the firm acquired US Script, a pharmacy benefits manager. The company later merged US Script with subsidiaries to form its Envolve divisions. In 2011, the firm formed Centurion, a provider of correctional health care services, as a joint venture with MHM Services. In 2018, it acquired MHM Services, including its stake in Centurion. Centene began offering state-run Medicaid programs through Affordable Care Act exchanges in 2014.
In July 2015, Centene announced it would acquire Health Net and Trillium Community Health Plan (serving Oregon). In March 2016, it finalized its acquisition. In September 2017, it announced that it would acquire Fidelis Care, a nonprofit insurer in New York, for US$3.75 billion. In March 2019, it announced plans to acquire WellCare for US$17.3 billion, a deal completed in January 2020. In January 2021, it was announced that it would acquire Magellan Health for $2.2 billion. In January 2022, the acquisition was completed.
In the United Kingdom, Centene began to acquire local healthcare services in 2017. In 2019, Centene, through its subsidiary MH Services, took a 40% stake in Circle Health, as part of a deal which created a national network of over 50 private hospitals. Centene gained full control of Circle Health in July 2021, and sold the business to PureHealth in August 2023.
In early 2021, Operose Health, a UK subsidiary of Centene, took over a group of London practices, AT Medics.
In May 2022, Centene sold off its pharmacy benefit management businesses, Magellan Rx and PANTHERx Rare, for a total of $2.8 billion.
In January 2023, Centene sold Centurion, and in December that year, sold Operose Health to HCRG Care Group.