After secondary school, Lang attended Red Deer College, where she became fascinated with the life and music of Patsy Cline and decided to pursue a career as a professional singer. She moved to Edmonton after her graduation in 1982 and formed a Patsy Cline tribute band called the Reclines in 1983. She and the Reclines recorded a debut album, Friday Dance Promenade, at Sundown Recorders. Label owner Larry Wanagas became her personal manager. The first band featured Stu Macdougal on keys, Dave Bjarnson on drums, Gary Koligar on guitar and Bassist Farley Scott.

The Reclines regularly played Edmonton's popular Sidetrack Cafe, a local venue that featured live bands six nights a week. In 1983, Lang presented a performance-art piece, a seven-hour re-enactment of the transplantation of an artificial heart for Barney Clark, a retired American dentist. A Truly Western Experience was released in 1984 and received strong reviews and led to national attention in Canada. In August 1984, Lang was one of three Canadian artists to be selected to perform at the World Science Fair in Tsukuba, Japan (along with other performing and recording contracts throughout Japan).

Lang made several recordings that received very positive reviews and earned a 1985 Juno Award for Most Promising Female Vocalist. She accepted the award wearing a wedding dress borrowed from her male roommate at the time. She also made numerous tongue-in-cheek promises about what she would and would not do in the Future, thus fulfilling the title of 'Most Promising'. She has won a total of eight Juno Awards.

In 1986, Lang signed a contract with an American record Producer in Nashville, Tennessee, and received critical acclaim for her 1987 album, Angel with a Lariat, which was produced by Dave Edmunds.

Lang performed several times on The Super Dave Osborne Show starting in 1987. In 1988 "k.d. lang and The Reclines" appeared on Austin City Limits. Lang played the lead in the 1991 drama film, Salmonberries, and also co-starred with Ewan McGregor and Ashley Judd in Eye of the Beholder (1999). She had an uncredited role as a lounge singer, performing the song "Love for Sale", in 2006's The Black Dahlia. She has also made guest appearances on the sitcoms The Larry Sanders Show, Dharma & Greg, and the famous coming out episode of Ellen. She appeared on the Christmas special of Pee Wee's Playhouse, where she performed the song "Jingle Bell Rock. " She also made a guest appearance on the "Garbage" episode of The Jim Henson Hour, and in 2008 appeared on Rove McManus' live hour show, Rove.

1988 marked the release of Shadowland, an album of torch country produced by Owen Bradley. In late 1988, Shadowland was named Album of the Year by the Canadian Country Music Association. That year she also performed "Turn Me Round" at the closing ceremonies of the XV Winter Olympics in Calgary, Alberta, and sang background vocals with Jennifer Warnes and Bonnie Raitt for Orbison's acclaimed television special, Roy Orbison and Friends, A Black and White Night.

In 1989, she sang a duet, "Sin City", with Dwight Yoakam on his album Just Lookin' for a Hit.

She is a vegetarian and an animal rights Activist. Her "Meat Stinks" campaign in the 1990s created much controversy, particularly in her hometown, in the middle of Alberta's cattle ranching industry—she was banned from more than 30 Alberta radio stations. A sign in Consort, Alberta, stating "Home of k.d. lang" was burned to the ground. Alberta's agriculture minister at the time said it was "extremely unfortunate that she has decided to side with the animal rightists. There's a certain feeling of betrayal – we have supported k.d. fairly well in Alberta." More than a dozen radio stations in the U.S. throughout Kansas, Oklahoma, Missouri, Montana and Nebraska also boycotted playing her records due to her "Meat Stinks" campaign.

Lang, who came out as a lesbian in a June 1992 article of the LGBT news magazine The Advocate, has championed gay rights causes.

Lang appeared on the cover of the August 1993 issue of Vanity Fair photographed by Herb Ritts. The cover featured Lang in a barber chair while model Cindy Crawford appeared to shave her face with a straight razor, which Lang would later say was inspired by the French film Le mari de la coiffeuse. The issue contained a detailed article about Lang which observed that she had thought that she would be ostracized by the country music industry when she came out as a lesbian. However, Nashville was accepting, and her records continued to sell.

In 1996, she was made an Officer of the Order of Canada.

In 1997, Drag, an album of cover tunes dedicated to 'smoke' (specifically cigarette smoking) was released. The album cover and booklet photographs show Lang in a man's suit, referring to crossdressing as another possible meaning of the word 'drag'. The songs on Drag include "Smoke Dreams, " from the '40s, Steve Miller Band's "The Joker, " "Smoke Rings, " the theme from the cult movie Valley of the Dolls, and 8 other smoke-themed songs. In 1998, she was inducted into the Canadian Lesbian and Gay Archives' National Portrait Collection.

In 1999, Lang ranked No. 33 on VH-1's 100 Greatest Women in Rock & Roll, and she ranked No. 26 on CMT's 40 Greatest Women in Country Music in 2002, one of only eight women to make both lists. (The others were Linda Ronstadt, Patsy Cline, Dolly Parton, Tammy Wynette, Loretta Lynn, Lucinda Williams, and Emmylou Harris).

In 2003, she won her fourth Grammy Award, this time for Best Traditional Pop Vocal Album for her collaboration with Tony Bennett on A Wonderful World.

Also in 2004, she sang the song "Little Patch of Heaven" for the Walt Disney Feature Animation film Home on the Range.

In 2006, she paired with singer Madeleine Peyroux on a cover of the Joni Mitchell song, "River", for Peyroux's album, Half the Perfect World. That same year Lang was featured in Nellie McKay's second album, Pretty Little Head, singing with McKay in "We Had it Right". As well, Lang sang a version of The Beatles' "Golden Slumbers" for the Happy Feet film Soundtrack. She also sang a duet with Ann Wilson on the Heart singer's solo album Hope & Glory covering the Lucinda Williams song "Jackson".

In 2007, she teamed up with one of her childhood idols, Anne Murray, on a remake of Anne's hit, "A Love Song", to be featured on Anne's album, Friends And Legends. The duet was recorded in Los Angeles, California.

In November 2005, Lang received the National Arts Centre Award, a companion award of the Governor General's Performing Arts Awards. On June 3, 2008, it was announced that she would receive a star on Canada's Walk of Fame.

On November 11, 2009, she entered into a domestic partnership with Jamie Price whom she had met in 2003. After separating on September 6, 2011, Lang filed for a dissolution of the partnership in Los Angeles County Superior Court in Los Angeles, California, on December 30, 2011.

On February 12, 2010, she performed Leonard Cohen's "Hallelujah" at the Olympics Opening Ceremony in Vancouver, British Columbia. In early May 2010, Lang filled in at the last minute for Susan Boyle at the Australian TV Logie Awards to reprise her Winter Olympics performance of Leonard Cohen's "Hallelujah", receiving an extended standing ovation. In 2010, she sang "You're a Mean One, Mr. Grinch" with Matthew Morrison in a Christmas episode of Glee, and is featured on Glee: The Music, The Christmas Album. In February 2013, she appeared in Season 8 of the CBS sitcom, How I Met Your Mother, as herself.

In 2011, Lang was inducted to Q Hall of Fame Canada in recognition of the work she has done to further equality for all peoples around the world.

In 2012, she moved from Los Angeles to Portland, Oregon.

On April 21, 2013, during the 2013 Juno Awards, Lang was formally inducted into the Canadian Music Hall of Fame. She is notable for praising Canadians and "letting your freak flags fly" during her acceptance speech.

Lang made her Broadway debut as the "Special Guest Star" in Broadway's After Midnight, replacing Fantasia Barrino and to be succeeded by Toni Braxton and Babyface. She appeared from February 11 to March 9, 2014.

Lang reflected on coming out in a 2016 interview with The Canadian Press, saying it "felt like it was the most responsible thing for society and myself" at the time. She also noted that dealing with the fallout was something she struggled with in the years that followed. "It's a very hard thing to unravel for me and decipher," she said. "In a way you can't. It's all just a big ball of wax of who I am and what my role in popular culture was — and what pop culture's role was in me."