Shepherd Brown, a native of Virginia, arrived in New Orleans in 1800 as an associate of Baltimore merchant William Taylor. Brown was also associated with two other Taylor colleagues, William O. Payne and John McDonogh. When their firm, McDonogh and Payne, dissolved in August, 1802, McDonogh and Brown launched two new ventures John McDonogh, Jr. and Company, and Shepherd Brown and Company. The former entity more or less continued the activities of the old firm, selling imported products. The Brown company meanwhile pursued the newly developing western trade, purchasing agricultural products from up river for eventual transshipment to eastern markets.

The relationship of McDonogh and Brown with William Taylor broke down during early 1805. In February of that year Shepherd Brown and Company was dissolved due at least in part to Brown's ill health. Following his retirement from the mercantile business, he concentrated on real estate and also held several governmental positions as well as membership on the board of the branch bank of the United States. Shepherd Brown died in Baltimore on February 7, 1818.