The question has a factual answer, and the two women usually offered as candidates are both the wrong one. One was never charged with murder. The other was acquitted.
Lavinia Fisher is the name that comes up first, and she is in this archive only because almost everything said about her is untrue. She and her husband John kept the Six Mile House, a roadside boarding house north of Charleston, South Carolina, which was one of two houses used by a gang robbing the wagon trade in and out of the city. By early 1819 those robberies were serious enough to demand a response.
In February 1819 vigilantes rode out, cleared the area and left a young man called David Ross to keep watch. The gang set on him the next morning and brought him before Lavinia Fisher, who, on the account that reached the court, took him by the throat and put his head through a window. He got away. A traveller named John Peeples arrived soon after looking for a room, was told there were none but invited in for tea, and was robbed. He escaped too, and reported it. The Fishers were arrested on February 18, 1819.
They were indicted for assault with intent to murder and common assault. The charge was then changed to highway robbery, a capital offence in South Carolina at the time, and that is what they were convicted of in May 1819. Historians have noted the irregularity: they were convicted of an offence they were never formally tried for. Both proclaimed their innocence to the end, and they were hanged in Charleston on February 18, 1820, a year to the day after the arrest. She was twenty-seven.
Nothing in that paragraph is a murder.
What most people know instead is the tea laced with poison, the bed on a hinge that tipped guests into a pit, and the cellar full of skeletons. None of it is in the trial record or in the contemporary newspapers. The pit is the easiest to dispose of: houses in the South Carolina Lowcountry do not have basements. The most quoted line in the whole story, that she told the crowd she would carry any message they had for the devil, comes from later retellings and has never been verified. Accounts cannot even agree on the wedding dress.
A grave was found in the woods near the house while the Fishers were awaiting their appeal. It held two bodies: a white man shot at about the time of the vigilante raid, and a young African American woman buried some two years earlier. Nobody was charged over either, and with the traffic through that house it was never possible to establish who was responsible. Two bodies. Not hundreds.
Nic Butler, a historian at the Charleston County Public Library, puts it plainly: the Fishers were real and there is a paper trail of their trial, conviction and execution, and it is completely different from the story that has been fictionalised. The fullest modern account is Bruce Orr's Six Miles to Charleston, written by a former Charleston-area homicide detective working from the documents.
The second candidate is Jane Toppan, and she has the opposite problem. She did it, and there is no conviction.
She trained as a nurse at Cambridge Hospital in 1885 and later at Massachusetts General, was well liked, called Jolly Jane, and was already killing. She altered patients' morphine and atropine doses, sometimes to kill and sometimes to bring them to the edge and back, and falsified their charts. Morphine constricts the pupils and atropine dilates them; she used the two together in part because the combination masks what a physician would look for. Both hospitals dismissed her over irregularities without any criminal accusation, and she moved into private nursing, which put her inside families.
In 1901 the Davis family of Cataumet on Cape Cod engaged her. Mattie Davis died at Toppan's lodgings in Boston. Toppan travelled down to help, and over the next six weeks Mattie's husband Alden and both their daughters died as well. A surviving son-in-law demanded a toxicological examination, which led to exhumations and to her arrest on October 29, 1901.
She confessed to thirty-one murders and said her ambition had been to have killed more people, helpless people, than any other man or woman who ever lived. Her trial lasted a day. The jury took under half an hour to find her not guilty by reason of insanity, and she was committed to the Taunton Insane Hospital, where she died in 1938. Only three deaths were ever formally charged. The thirty-one is her own count, and most historians of the case think it plausible and possibly low.
So one woman has a hanging and no murder charge, and the other has a confession and an acquittal. Neither is a serial murder conviction, and the honest answer to the title is that the question is being settled by storytelling rather than by records.
If the test is a woman convicted of multiple murders in the United States, there is a better answer, and she is two decades earlier than Toppan.
Lydia Sherman poisoned her first husband, Edward Struck, with arsenic in his gruel in 1864, after he lost his job and took to drink and to his bed. She said later that he had become useless to the family and she could not feed the children. She then killed the children, six of them over the following year, one after another, recorded by doctors as remittent fever and bronchitis. She moved to Connecticut, married an elderly farmer who died within fourteen months leaving her his property, then married a widower named Nelson Sherman, whose baby, whose daughter and finally whose own life followed by May 1871.
A doctor who had attended Sherman was not satisfied. He kept the liver and had it analysed at Yale, and it was full of arsenic. She was tried at New Haven in April 1872, convicted of second degree murder and sentenced to life. From prison she gave a newspaper a written confession listing eleven deaths, which was printed and sold. She died at Wethersfield in 1878.
A conviction, a confession and eleven deaths, running from 1864, which is twenty-one years before Toppan arrived at Cambridge Hospital already killing, and forty-four after Lavinia Fisher was hanged for robbery.
Even that is not a safe answer, and it should not be offered as one. The question depends on what counts as a series, on which deaths were investigated at all, and on the records of a century in which a poisoned wife or child was very often written up as fever. What can be said is narrower and more useful. Two women are offered the title constantly, and neither of them has a murder conviction. A third, who has one, is not offered it at all.