Operating primarily in Maryland, Harker played a significant role in the domestic slave trade, actively engaging in the buying and selling of enslaved African Americans from 1835 to 1859.

Harker's operations were deeply embedded in the economic landscape of the Southern United States, reflecting the demand for enslaved labor and the profitability of the trade.

As historian Frederic Bancroft noted in Slave Trading in the Old South (1931): William Harker was a remarkable exception, for he was 'in the market' for a quarter of a century—1835–59, and he bought 'all likely negroes from 8 to 40 years of age'.

Persons having negroes that are slaves for life to dispose of will find it to their interest to see me before they sell, as I am determined to pay the highest prices in cash that the Southern market will justify.

It is a mere matter of taste, to be sure; but then, some well-disposed people like to see it on a trader's card, thinking it has a more creditable appearance; and, probably, Mr. Harker, if he reflects a little, will put it in next time.