He earned his fortune as an owner of business interests beginning in the 1830s originally as a hardware wholesaler, and later expanding into railroads, banking and finance, iron works, and steamship lines and other transportation companies.

[2] In 1851, Pratt and his partner invested in western Maryland coal mines and iron yards in the expanding and developing industrial and commercial Baltimore neighborhood of Canton.

Pratt also became president of the Baltimore Clearing House and the Maryland Bankers' Association, in addition to establishing a role in several transportation companies.

[2] He founded the "House of Reformation and Instruction for Colored Children" which he offered on his former farm property at Cheltenham (in Prince George's County),[2] and the Maryland School for the Deaf and Dumb located at Frederick on South Market Street.

Further, he requested that to Mayor William Pinkney Whyte and the Council continue an annual appropriation to the new library system and support it in the years to come to supplement the interest and benefits accumulating from the principal of his bequest.

His intention was to establish a library that "shall be for all, rich and poor without distinction of race or color, who, when properly accredited, can take out the books if they will handle them carefully and return them."

After four years of plans, construction and the hiring of staff with the purchasing of many books, the new library was ready to be opened in January 1886 with some appropriate addresses at ceremonies at the nearby luxurious auditorium of the Academy of Music on North Howard Street (between West Centre and West Franklin Streets), and opened to new patrons and business at the beginning of February 1886.

"[2] Pratt's bequest was used to complete construction of the old Moses Sheppard Asylum, enlarge the facility to house 200 additional patients at its country campus in western Towson, further north of the city off (North) Charles Street Avenue in suburban Baltimore County, at the old "Mount Airy Farm" of Baltimore merchant Thomas Poultney, which they purchased in 1858 and began construction two years later, however not opening until 1891, trying to remain faithful to the original directions to serve the indigent.

Enoch Pratt's city townhouse/mansion located at 201 West Monument Street (southwest corner with Park Avenue in Mount Vernon-Belvedere, purchased in 1847).

[10] A research library, archives, and underground storage stacks were constructed in the following decade at the southern rear of the mansion replacing the former carriage house.