He began his business career in driving herds of livestock to the mid-west for sale, at the same time buying up land for re-sale. He became known as a livestock breeder and seller. Millikin moved to Decatur in 1856 and made his new home there, getting married the next year.
Later, Millikin became a local banker and helped found Millikin University. When the college opened in 1903, the inaugural address was made by President Theodore Roosevelt.
He died in Orlando, Florida, on February 25, 1909. His funeral was held at Millikin University in Decatur, Illinois, and he was buried in Greenwood Cemetery in Decatur.
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