The sisters were also introduced to the recently-widowed railroad magnate, Cornelius Vanderbilt, with Woodhull becoming his soothsayer and Tennessee Claflin his mistress. In September 1869, Woodhull relied on inside information from a well-connected friend to give Vanderbilt advice, under the guise of a séance, on investing and disinvesting in the gold market. Following her advice, Vanderbilt made a profit of $1.3 million on the gold market, withdrawing just before its crash of Black Friday, September 24. It was rumored that Vanderbilt carried through on a promise to share half of any gain with Woodhull. Whether or not he did, Vanderbilt did finance the establishment of Woodhull, Claflin, & Co.

In late 1869, Woodhull and Claflin rented two rooms at the posh Hoffman House at 44 Broad Street, and in January 1870, sent out calling cards announcing their new brokerage. The office was elegantly furnished, and included a portrait of Vanderbilt displayed prominently. In addition to financial and political titans such as Vanderbilt, Jim Fisk, and William "Boss" Tweed, the official opening on February 14 was besieged by so many throngs of the curious that 100 police officers had to keep order.

The female-focused brokerage also caused a sensation in the press. "Wall-Street Aroused," announced The New York Times, which went on to question their potential for success, not because they were women, but because of their association with spiritualism and other unorthodox causes. This Harper’s Weekly cartoon follows the lead of the dailies in dubbing them "Bewitching Brokers," but the news department doubted that there was a sufficient number of women with money to invest for the firm to be successful.

On the contrary, despite limited opportunities for women’s employment and continuing pay inequity, Woodhull and Claflin had hit upon an untapped source of investment capital. Society wives and widows, teachers, small-business owners, actresses, and high-priced prostitutes and their madams sought the company of the sisters (in the women-only backroom) and the advice of Woodhull’s current husband, Colonel James Harvey Blood, and brother-in-law, George Blood (transacting the actual business in the front room). The firm was an immediate financial triumph. It allowed the sisters to rent an expensive apartment in the exclusive Murray Hill section of Manhattan, and to entertain royally the famous and the powerful, particularly fellow freethinkers like Congressman Benjamin Butler.

The brokerage profits also underwrote the sisters’ newspaper and Woodhull’s presidential campaign. Three months to the day after opening the brokerage (May 14, 1870), the first issue of Woodhull & Claflin’s Weekly was published (with Colonel Blood as managing editor). It was dedicated to disseminating their radical reform agenda, including Free Love—the promotion of sexual freedom within or without marriage, and birth control. Tennessee Claflin, soon joined by her sister, broke other sexual taboos by wearing men’s apparel—business jacket, vest, and tie—with shorter, ankle-length skirts. In 1871, Woodhull presented a petition for women’s voting rights to Congress and became a leader in the women’s suffrage movement. In 1872, she became the first woman to be nominated for president, running on the Equal Rights ticket.

Also in 1872, however, Woodhull suffered a series of setbacks which caused her downfall. Harper’s Weekly cartoonist Thomas Nast attacked the Free Love advocate as the embodiment of Satan. [See the archive for the cartoon of February 17, 1872, " Get Thee Behind Me, (Mrs.) Satan."] Civic groups across the country which had been eager to hear the thoughts of this unconventional women, canceled her speaking engagements. She lost popularity with fellow radicals when German-American members of the IWA criticized her and others for emphasizing feminism, temperance, and spiritualism. Vanderbilt withdrew his financial support of the brokerage house after Woodhull’s mother ineptly tried to blackmail him. Anti-vice crusader Anthony Comstock condemned the sisters’ newspaper as immoral. The journal’s revelation of an adulterous affair between noted evangelist Henry Ward Beecher and the wife of Woodhull’s biographer brought the sisters further negative publicity. The already weakened brokerage went under when an economic depression began in 1873.