Built by the architects York and Sawyer, the 41st Street building contained areas for talks, meetings, and dinners, living and laboratory spaces that could be rented by members, and a world-class chemical research library.

[1]: 3–4 In 1898 Charles F. McKenna, William McMurtrie, Marston T. Bogert and others formed an organizational committee, and raised money to rent an available property at 108 West 55th Street.

[4]: 12–13  Committee chairperson Charles F. Chandler, a professor at Columbia University, donated $1000 to the fledgling organization and became its first president.

[1]: 3–4 [5]: 409 [6] As of November 29, 1898, the club had 154 charter members, including Leo Baekeland, Edward G. Love, William H. Nichols and Maximilian Toch.

He was determined to create a permanent space for the Chemists' Club, and actively campaigned to raise money for the project.

The Chemists Building Company was subsequently formed, and sold shares of stock to help finance the project.

The building was "an artistic structure of white marble, in the style of the French Renaissance of the Louis XVI period, finished with Ionic pilasters and balconies at the second story and similar decorative balconies at the top story.”[2] The New York Times called the building “absolutely unique in the world”.

[2] The organization was determined to make spaces available for those who would otherwise not have access to the resources they needed: "for the young man whose income is still small, for the technical man who wants library facilities, for the teacher who is primarily interested in the scientific side of his work, and at the same time in retaining the interest and support of the business man, the executive and sales manager who wants a Club to which he is glad to bring his friends and business acquaintances.

It included a hexagonal benzene ring for organic chemistry, crossed retorts for distillation, and a salamander surrounded by fire, in red and gold.

The redesign has preserved many original features of the building, including the boardroom, which has been restored as the Alchemy Suite.

In 1904, the Club hosted the first annual meeting of the London-based Society of Chemical Industry to be held outside Great Britain.

An article in Industrial & Engineering Chemistry describes the need for such space: "A chemist with his laboratory is not welcome as a tenant in modern, high class, centrally located and well equipped buildings, and, as a result, in most of the cities, and particularly in New York, the chemist and his laboratory are crowded into the less desirable sections of the city, and then only in the less desirable buildings.

[5]: 410 A major impetus for forming the Club was the desire to house the library of the American Chemical Society and make the collection available to working chemists.

The library eventually absorbed a number of private collections including those of Charles F. Chandler, J. Meritt Matthews,[18] John Mallet, Herman Frasch,[19] Morris Loeb and Hugo Schweitzer.

“One of the special features of the building is the board room, which has been fashioned to represent a laboratory in the days of alchemy” with “vaulted roof, flag-stoned floor, iron-bound chest, high writing desk—even the fireplace with strange black pots and alembics upon it, and, overhead, just outside the door, a winding stone stairway just like those by which the wizards of the black arts used to steal away from prying eyes to juggle with fire and crucibles, transmute base metals to gold, conjure up devils, and otherwise qualify for execution at the hands of the public hangman.”[2] Another feature of the room was the stuffed alligator hanging from the ceiling, in homage to the alchemists' iconographic salamander, which could live in fire without burning.

In response to the Depression, a Committee for the Relief of Unemployed Chemists and Chemical Engineers opened an office at the club in 1932.

[1]: 6, 14 For much of its history, in practice and at times by definition, membership in the Chemists' Club was open only to "male persons".

In 1921, the Club's Bureau of Employment expressed concern, in its yearly report, that women chemists were being laid off in the wake of World War I.

"Another phase repeatedly brought to our notice is the decrease in willingness to consider the employment of woman chemists.

The second woman to join was E. Janet Berry, a chemist and expert in patent law who became a member of the Club's board of directors.