Christine graduated from Christopher Columbus High School in 1945 and was soon drafted into the U.S. Army at the age of 19. After being discharged from the Army, Jorgensen attended Mohawk Valley Community College in Utica, New York, the Progressive School of Photography in New Haven, Connecticut, and the Manhattan Medical and Dental Assistant School in New York City. She also worked briefly for Pathé News.

She obtained special permission from the Danish Minister of Justice to undergo a series of operations in that country. On September 24, 1951, surgeons at Gentofte Hospital in Copenhagen performed an orchiectomy on Jorgensen. In a letter to friends on October 8, 1951, she referred to how the surgery affected her:

In November 1952, doctors at Copenhagen University Hospital performed a penectomy. In Jorgensen’s words, “My second operation, as the previous one, was not such a major work of surgery as it may imply.”

The New York Daily News ran a front-page story on December 1, 1952, under the headline “Ex-GI Becomes Blonde Beauty”, announcing (incorrectly) that Jorgensen had become the recipient of the first “sex change”. This type of surgery had previously been performed by German doctors in the late 1920s and early 1930s. Dorchen Richter and Danish artist Lili Elbe, both patients of Magnus Hirschfeld at the Institut für Sexualwissenschaft in Berlin, were known recipients of such operations in 1930–31. What was different in Jorgensen’s case was the added prescription of female hormones.

After her surgeries, Jorgensen originally stated that she wanted a quiet life of her own design, but once returning to the United States, the only way she could manage to earn a living was by making public appearances. Jorgensen was an instant celebrity when she returned to New York in February 1953. A large crowd of journalists met her as she came off her flight, and despite the Danish royal family being on the same flight, they were largely ignored in favor of her. Soon after her arrival, she launched a successful nightclub act and appeared on TV, radio, and theatrical productions. The first of a five-part authorized account of her story was written by Jorgensen herself in a February 1953 issue of The American Weekly, titled “The Story of My Life” and in 1967, she published her autobiography, Christine Jorgensen: A Personal Autobiography, which sold almost 450 thousand copies.

After her vaginoplasty, Jorgensen planned to marry labor union statistician John Traub, but the engagement was called off. In 1959 she announced her engagement to typist Howard J. Knox in Massapequa Park, New York, where her father had built her a house after her reassignment surgery. However, the couple were unable to obtain a marriage license because Jorgensen’s birth certificate listed her as male. In a report about the broken engagement, The New York Times reported that Knox had lost his job in Washington, D.C., when his engagement to Jorgensen became known.

After her parents died, Jorgensen moved to California in 1967. She left behind the ranch home built by her father in Massapequa and settled at the Chateau Marmont in Los Angeles, California, for a period of time. It was also during this same year that Jorgensen published her autobiography, Christine Jorgensen: A Personal Autobiography, which chronicled her life experiences as a transsexual and included her own personal perspectives on major events in her life.

The Christine Jorgensen Story, a fictionalized biopic based on Jorgensen’s memoir, premiered in 1970. John Hansen played Jorgensen as an adult, while Trent Lehman played her at age 7.

Jorgensen also worked as an actress and nightclub entertainer and recorded several songs. In summer stock, she played Madame Rosepettle in the play Oh Dad, Poor Dad, Mamma’s Hung You in the Closet and I’m Feelin’ So Sad. In her nightclub act, she sang several songs, including “I Enjoy Being a Girl”, in which, at the end, she made a quick change into a Wonder Woman costume. She later recalled that Warner Communications, owners of the Wonder Woman character’s copyright, demanded that she stop using the character; she did so, and instead used a new character of her own invention, Superwoman, who was marked by the inclusion of a large letter S on her cape. Jorgensen continued her act, performing at Freddy’s Supper Club on the Upper East Side of Manhattan until at least 1982, when she performed twice in the Hollywood area: once at the Backlot Theatre, adjacent to the discothèque Studio One, and later at The Frog Pond restaurant. This performance was recorded and has been made available as an album on iTunes. In 1984, Jorgensen returned to Copenhagen to perform her show and was featured in Teit Ritzau’s Danish transsexual documentary film Paradiset er ikke til salg (Paradise Is Not for Sale). Jorgensen was the first and only known trans woman to perform at Oscar’s Delmonico Restaurant in downtown New York, for which owners Oscar and Mario Tucci received criticism.

She died of bladder and lung cancer in 1989, four weeks short of her 63rd birthday. Her ashes were scattered off Dana Point, California.

In Christine Jorgensen Reveals, a stage performance at the 2005 Edinburgh Festival Fringe, Jorgensen was portrayed by Bradford Louryk. To critical acclaim, Louryk dressed as Jorgensen and performed to a recorded interview with her during the 1950s while video of Rob Grace as comically inept interviewer Nipsey Russell played on a nearby black-and-white television set. The show went on to win Best Aspect of Production at the 2006 Dublin Gay Theatre Festival, and it ran Off-Broadway at New World Stages in January 2006. The LP was reissued on CD by Repeat The Beat Records in 2005.

Transgender historian and critical theorist Susan Stryker directed and produced an experimental documentary film about Jorgensen, titled Christine in the Cutting Room. In 2010 she also presented a lecture at Yale University titled “Christine in the Cutting Room: Christine Jorgensen’s Transsexual Celebrity and Cinematic Embodiment”. Both works examine embodiment vis-à-vis cinema.

In 2012 Jorgensen was inducted into the Legacy Walk, an outdoor public display which celebrates LGBT history and people.

In 2014, Jorgensen was one of the inaugural honorees in the Rainbow Honor Walk, a walk of fame in San Francisco’s Castro neighborhood noting LGBTQ people who have “made significant contributions in their fields”.

The 2016 book Andy Warhol was a Hoarder: Inside the Minds of History’s Great Personalities, by journalist Claudia Kalb, devotes a chapter to Jorgensen’s story, using her as an example of gender dysphoria and the process of gender transition in its earliest days.

In June 2019, Jorgensen was one of the inaugural 50 American “pioneers, trailblazers, and heroes” included on the National LGBTQ Wall of Honor within the Stonewall National Monument (SNM) in New York City’s Stonewall Inn. The SNM is the first U.S. national monument dedicated to LGBTQ rights and history, and the wall’s unveiling was timed to take place during the 50th anniversary of the Stonewall riots.