She was selected to compete at the international Tahitian Dance Competition in San Jose, California in 1996 and 1997. She performed in over fifty professional dance performances island wide. As member of the Waikiki Singers, she was chosen to be the Soprano Soloist, performing Schubert's Mass in G and Amahl and the Night Visitors by Gian Carlo Menotti. At the age of six years, Kilcher was the first child to study classical voice at the University of Hawaii with Laurance Paxton. She also studied Drama with Bill Ogilvie at the Diamond Head Theater. At six years, her mother booked her at venues as featured singer and opening act to some of Hawaii's greats, such as Willie K. (Kahaiali'i) among others.

When Kilcher was two years old, she and her mother moved to Kapaʻa, Hawaii, where her brother Kainoa was born. Her father, from whom she is estranged, was absent for much of her life. Growing up in Hawaii, Kilcher was inspired by the local culture and started hula dancing at the age of five years. She also trained in Tahitian dance and West African, as well as ballet, Hip Hop and Modern Dance. In 1997 Kilcher won Ballet Hawaii's Young Choreographer Award at the age of seven years.

In 1999, her mother moved the family to California. Kilcher started to showcase her talent busking on the Third Street Promenade in Santa Monica.

At 14, Q'orianka emerged into the front ranks of young actors with her portrayal of Pocahontas opposite Colin Farrell and Christian Bale in Director Terrence Malick Academy Award-nominated motion picture, The New World (2005). Her performance was critically acclaimed and won her the National Board of Review's best breakthrough performance of 2006, the 2006 Alma Award for best Latin American Actress in a feature film, numerous other award nominations. The film was released in December 2005 to mixed reviews. The film was a critical success, receiving several positive reviews and award nominations, but it was shown in only 811 theatres worldwide. It yielded a relatively low box office gross.

In the summer of 2006, Kilcher began filming the independent film The Power of Few, which she produced through her own production company, Entertainment On-Q. She played the title role in the feature film Princess Kaiulani. The film, about the United States' overthrow of the Hawaiian monarchy, was released in May 2010 to negative reviews. However, Kilcher received positive feedback for her role, with Roger Ebert writing that "she evokes great depth and sympathy in her role and seems to have created Kaiulani from the inside out."

On June 11, 2009 she visited Lima to support indigenous peoples' rights in the Amazon Bagua, Peru. In 2007, Kilcher won the Brower Youth Award, a premier environmental award, for her work in persuading Occidental Petroleum to withdraw from the Peruvian Amazon valley. She received the Young Hollywood Green Award.

On June 1, 2010, Kilcher and her mother were arrested after Kilcher chained herself to the gates in front of the White House in Washington, D.C. while her mother poured black paint on her to signify oil. Kilcher was protesting President Barack Obama's meeting with Peruvian President Alan García, accusing him of selling land in the Amazon rainforest to corporations while suppressing indigenous protests. She and her mother were charged with disorderly conduct. The charges were dropped on June 6, 2011 after they completed community Service.

In 2011, Kilcher played Tiger Lily in Neverland, a version of the Peter Pan story that aired on the Syfy Channel.

In 2013, Kilcher portrayed Rayen in Running Deer, an award-winning short film produced and directed by Brent Ryan Green through Toy Gun Films.

On September 4, 2015, Kilcher joined with Natasha Bedingfield, Sean Paul, Paul McCartney, Fergie, Colbie Caillat, Krewella, Angelique Kidjo, Christina Grimmie, Kelsea Ballerini, Victoria Justice, Nicole Scherzinger, Sheryl Crow and Toby Gad for the environmentally-themed "Love Song to the Earth." The song aims at raising awareness of climate change, with all proceeds benefiting Friends of the Earth U.S. and the UN Foundation. Kilcher and several Love Song Singers performed in Washington, DC ahead of Pope Francis' address to the U.S. Congress.