Historical accounts of transgender people in the land now known as the United States of America date back to at least the early 1600s. Before Western contact, some Native American tribes had third gender people whose social roles varied from tribe to tribe. People dressing and living differently from the gender roles typical of their sex assigned at birth and contributing to various aspects of American history and culture have been documented from the 17th century to the present day. In the 20th and 21st centuries, advances in gender-affirming surgery as well as transgender activism have influenced transgender life and the popular perception of transgender people in the United States.

Overview Prior to 1800

Some Native American Nations have longstanding names and roles for gender-variant or third-gender people. The term two-spirit, which is now retroactively used to describe these historical roles, was only created in 1990 at the Indigenous lesbian and gay international gathering in Winnipeg, and "specifically chosen to distinguish and distance Native American/First Nations people from non-Native peoples". The primary purpose of coining a new term was to encourage the replacement of the outdated and considered offensive, anthropological term, berdache, which appears in anthropological accounts. While this new term has not been universally accepted—it has been criticized by traditional communities who already have their own terms for the people being grouped under this new term, and by those who reject what they call the "western" binary implications, such as implying that Natives believe these individuals are "both male and female"—it has generally received more acceptance and use than the anthropological term it replaced.

One of the first documented inhabitants of the American colonies to challenge binary gender roles was Thomas(ine) Hall, a servant who, in the 1620s, alternately dressed in both men's and women's clothing. Hall is likely to have been intersex, and was ordered by the Virginia court to wear both a man's breeches and a woman's apron and cap at the same time.Genny Beemyn, "Transgender History in the United States", from Trans Bodies, Trans Selves, edited by Laura Erickson-Schroth, Oxford University, 2014, p.1 Ellen Hartigan-O'Connor, Lisa G. Materson, The Oxford Handbook of American Women's and Gender History (2018, ), pages 315–316

In 1776, the preacher Public Universal Friend reported experiencing death and returning to life as a genderless being (neither male nor female). After the Friend's purported resurrection, the Friend no longer answered to former birth name and gendered pronouns, dressing androgynously and asking followers they gained while preaching throughout New England over the next four decades to avoid birth name and gendered pronouns..Susan Juster, Lisa MacFarlane, A Mighty Baptism: Race, Gender, and the Creation of American Protestantism (1996, ), pp. 27-28; and Susan Juster, "Neither male nor female", in Possible Pasts: Becoming Colonial in Early America, pp. 362-363.Douglas L. Winiarski, Darkness Falls on the Land of Light (2017, ), p. 430. Some scholars have viewed them as outside the gender binary, and as a chapter in trans history "before [the word] 'transgender.Scott Larson, "Indescribable Being": Theological Performances of Genderlessness in the Society of the Publick Universal Friend, 1776–1819, Early American Studies (University of Pennsylvania Press), volume 12, number 3, Fall 2014, pp. 576–600.Rachel Hope Cleves, Beyond the Binaries in Early America: Special Issue Introduction, Early American Studies 12.3 (2014), pp. 459–468.The Routledge History of Queer America, edited by Don Romesburg (2018, ), esp. § "Revolution's End".

Generally, according to Genny Beemyn in a Transgender History of the United States, the few historical accounts of transgender people that exist in 17th and 18th century America predominantly feature female to male transgender people, possibly because it was more difficult for male to female people to successfully present as women before the advent of hormone treatments and gender-affirming surgery. One example she cites is Mary Henly, a female-assigned individual in Massachusetts who was charged with illegally wearing men's clothing in 1692 because it was "seeming to confound the course of nature".Genny Beemyn, "Transgender History in the United States", from Trans Bodies, Trans Selves, edited by Laura Erickson-Schroth, Oxford University, 2014, p.4

1800–1950 Joseph Lobdell (born in 1829 as Lucy Ann Lobdell) lived as a man for sixty years and due to this was arrested and incarcerated in an insane asylum. He was, however, able to marry a woman.

Stagecoach driver Charley Parkhurst (born in 1812) ran away from a Lebanon, New Hampshire orphanage at age 12 and lived as a man for the rest of his life. He was a celebrated carriage driver, spending some of his career serving frontier California during the Gold Rush. For at least 15 years he worked as a chicken farmer and lumberjack, and he managed to retire in Watsonville, California. He died from tongue cancer in 1879 while living alone in a cabin. He did not marry, and he was only outed by neighbors after his death.

Mary Jones (born in 1803 as Peter Sewally), a free African-American, was arrested in New York City in 1836 for dressing as a woman, prostitution, and pickpocketing. According to a contemporary report in the New York World, Jones appeared in court "attired a la mode de New York, elegantly, and in perfect style. Her dingy ears were decked with a pair of snow white earrings, her head was ornamented with a wig of beautiful curly locks, and on it was a gilded comb, which was half hid amid the luxuriant crop of wool." When asked about the dress, Jones replied, "I have been in the practice of waiting upon Girls of ill fame ... and they induced me to dress in Women's Clothes, saying I looked so much better in them and I have always attended parties among the people of my own Colour dressed in this way – and in New Orleans I always dressed in this way." Jones was sentenced to five years in prison for grand larceny. A lithograph titled "The Man-Monster", showing Jones in female clothing, was published shortly afterwards. Jones was arrested twice more in 1845, both times dressed as a woman.

During the American Civil War (1861–1865) at least 240 people who were assigned female at birth are known to have worn men's clothing and fought as soldiers. Many may have done so because they were not allowed to fight as women and this was their means of participating in the war effort. Some were transgender and continued to live as men throughout their lives. One such notable soldier was Albert Cashier, who lived as a man for over 53 years. After the war, Frances Thompson (a formerly enslaved black trans woman) was one of five black women who testified before Congress's investigation of the Memphis riots of 1866, during which a mob of white terrorists attacked and raped Thompson; ten years later, Thompson was arrested for "being a man dressed in women's clothing".Rosen, Hannah. Terror in the Heart of Freedom: Citizenship, Sexual Violence, and the Meaning of Race in the Postemancipation South. Chapel Hill: University of North Carolina Press, 2009.Ellen Hartigan-O'Connor, Lisa G. Materson, The Oxford Handbook of American Women's and Gender History (2018, ).

Transgender studies in Europe, especially Germany, began to percolate back to the United States in the late 1800s. Writer Edward Charles Spitzka reminded American readers of Edward Hyde, 3rd Earl of Clarendon, governor of colonial New York remembered for cross-dressing.

In 1895 a group of self-described androgynes in New York organized a club called the Cercle Hermaphroditos, based on their wish "to unite for defense against the world's bitter persecution". Jennie June (born in 1874, birth name unknown, also wrote under the pseudonyms Earl Lind and Ralph Werther), a member of the Cercle Hermaphroditos, wrote memoirs: The Autobiography of an Androgyne (1918) and The Female Impersonators (1922). June described himself with contemporary terms for gender and sexual variance as an invert, urning, fairie, androgyne, and "instinctive female impersonator". June was assigned male at birth and referred to himself with he/him pronouns throughout his memoirs, but said he had desired all his life to become a woman, and chose to have an orchiectomy (removal of the testicles) in order to help feminize his body. His stated purpose in publishing these very personal stories was to help increase acceptance of inverts, and reduce the suicide of young inverts.Meyerowitz, J. "Thinking Sex With An Androgyne". GLQ: A Journal of Lesbian and Gay Studies 17.1 (2010): 97–105. Web. Retrieved April 13, 2017. In 2010 five sections of her third volume of memoirs (dated 1921 but never published), previously lost, were discovered and published on OutHistory.org.

Murray Hall (1841–1901) was a politician in New York City for almost twenty-five years. After Hall's death, it was discovered that he had been assigned female at birth. Hall had been married twice and had an adopted daughter. Although his most recent wife had predeceased him, his daughter was described as "terribly shocked. She said she always believed her foster father was a man, and never heard her foster mother say anything that would lead her to suspect otherwise."

Some cases are known of immigrants changing their gender identity upon arrival in the United States, especially trans men. One notable case is that of Frank Woodhull, who lived for around 15 years as a man and was discovered to have been "posing as a man" during processing at Ellis Island in 1908.

In 1917, Dr. Alan L. Hart, working with psychiatrist Dr. Joshua Gilbert, was the first documented trans man in the United States to undergo hysterectomy and gonadectomy, in order to live his life as a man.Brian Booth. "Alberta Lucille Hart / Dr. Alan L. Hart: An Oregon 'Pioneer. Oregon Cultural Heritage Commission 2000. Retrieved October 31, 2016 Following his transition, Hart told The Albany Daily Democrat that he was "happier since I made this change than I ever have been in my life, and I will continue this way as long as I live ... I have never concealed anything regarding my [change] to men's clothing ... I came home to show my friends that I am ashamed of nothing."

Trans woman Lucy Hicks Anderson was born in 1886 in Waddy, Kentucky. She served as a domestic worker in her teen years, eventually becoming a socialite and madame in Oxnard, California during the 1920s and 1930s. In 1945, she was tried in Ventura County for perjury and fraud for receiving spousal allotments from the military, as her dressing and presenting as a woman was considered masquerading. She lost the case, but avoided a lengthy jail sentence, only to be tried again by the federal government shortly thereafter. She also lost this case, and was sentenced to jail time, along with her then husband Ruben Anderson. After serving their sentences, they relocated to Los Angeles, where they lived quietly until her death in 1954.

In 1933, Hannah Nokes, a Black trans woman born in 1898, made headlines when she testified in a court in Loudoun County, Virginia. Nokes was a witness for the prosecution at the historic trial of George Crawford, who was defended by an all-Black team including noted civil rights attorney Charles Hamilton Houston.