In the early 1980s, Billings worked under the stage name Shante at the famed Baton Show Lounge in Chicago, Illinois. Winning a series of beauty contests, she was named Miss Wisconsin, Miss New York, Miss Chicago, Miss Illinois, and Miss Florida. She also served as a judge of the Miss Continental pageant in 2000 and 2001.

Billings has been living with HIV since 1994, and has been an advocate for HIV health initiatives, as well as trans issues and trans rights. When talking about her fight to battle AIDS, she says that she believes the reason she has survived all these years is because of her wife who stood by her, loved her, and supported her through it all. She has spoken about her status in a number of interviews, including a 2016 article with her hometown paper. She also spoke to POZ Magazine for a 2003 interview about life with HIV.

Billings lives in Hollywood, California with her wife Chrisanne, whom she initially met at age sixteen in drama class. They were married in a commitment ceremony in Chicago on December 4, 1995. Billings was chosen as the Grand Marshal for the Pride Parade in Chicago, Illinois on June 28, 2009.

More recently, Billings has appeared in an autobiographical show, "S/He and Me." In the early 2000s, WTTW, the PBS station in Chicago, produced a documentary about Billings' life and career, "Schoolboy to Showgirl: The Alexandra Billings Story."

She has taught Viewpoints at the Steppenwolf Summer School since 2002 as well as taught at Louis University, The University of Chicago, Illinois University,the Illinois Theatre Convention, Act One Studios, and various classes and workshops around the Chicago area. Currently, she teaches at the Steppenwolf School West in Los Angeles California. Billings is currently a professor at the University of Southern California in Los Angeles, California where she is a Theatre professor. Before working at USC, she was an assistant professor at California State University, Long Beach. She received her MFA from CSULB, and delivered the commencement speech for CSULB College of the Arts in 2015.

Billings is also a professional singer who performs in theaters and nightclubs throughout the United States. She recorded her second CD The Story Goes On in 2003. She was a recipient of the New York MAC Hanson Award for Cabaret Artist of the Year in 2004.

She has appeared in the 2005 made-for-TV movie Romy and Michelle: A New Beginning. She has also played transgender characters in episodes of Karen Sisco, ER, Eli Stone, How to Get Away with Murder and Grey's Anatomy.

In 2010, Billings appeared in the film FAUX, in which she commented on gay marriage spurring the economy.

Billings' father, Robert Billings, was a music Teacher at Los Angeles Harbor College and the musical Director for the Los Angeles Civic Light Opera, which influenced her interest in theater. She assisted, working backstage with Carol Burnett and Yul Brynner. She also appeared in Jesus Christ Superstar and The Roar of the Greasepaint—the Smell of the Crowd. In her early life, Billings struggled with homelessness, prostitution, and cocaine and opioid addiction.

In 2015, Billings appeared on season two, episode six of How to Get Away with Murder as Professor Jill Hartford.

Alexandra Billings is an AIDS and LGBTQ Activist who argues for the equality of the LGBTQ community and urges others to use their voices to create change within the LGBTQ community. In 2016, Billings was awarded the Human Rights Campaign Visibility Award, which recognizes outstanding members of the LGBTQ community who live openly and freely in the public eye. After receiving the award, Billings thanked the audience, but also said, “I look around and I see you all and I cannot tell you how grateful I am that you’re here, and I have to say something to you I think you look great, you look swell and it’s wonderful that you’re here eating the chicken it’s delightful but I must tell you that we have to do something more than sit and speak and talk to our neighbors and eat great food and put on fancy clothes.” She challenges the audience to use their voices to speak loudly in order to create change and ultimately, equality for the LGBTQ community. In 2017, Transparent, the hit TV show Billings stars in, won the GLAAD Media Award for Outstanding Comedy Series. When accepting the award on behalf of the cast, Billings urges the audience to talk to people who disagree with their beliefs in order to spark conversation and create change instead of staying complacent. Specifically, she calls out the older LGBTQ generation and asks them to guide the younger LGBTQ generation because they will be the ones continuing the fight for equality in the Future. When delivering the commencement speech to the graduating class of the University of California State, Long Beach in 2015, Billings once again emphasized the importance of voice when she told the students that it is their job is to speak loud, big, and wide in order to spread their voices.

In 2017, transgender actors and actresses, including Billings (with the help of GLAAD and ScreenCrush), were part of a film to Hollywood written by Jen Richards, asking for more and improved roles for transgender people.