In 1857, at the age of twenty-six, his father gave him $500 in cash, and he moved to Ohio City, Kansas, where he opened a retail store.

He moved to Denver, Colorado to open a new retail store on Blake Street, trading supplies for livestock from new immigrants, then fattening them on the open range and using the profits to buy land in northeast Colorado, creating the largest ranch in Colorado history, where he raised as many as 35,000 heads a year to sell to Union Pacific construction crews, becoming a millionaire known as "the Cattle King of the Plains", leaving his fortune to found Iliff School of Theology.

When he died, Iliff's empire included 15,558 acres of prime land and 26,000 head of cattle, worth millions today.

[3] He became the largest and most successful cattle entrepreneur the west had ever produced.

"No man was ever known on the frontier who had Mr. Iliff's genius for handling cattle and conducting successfully large operations.