During high school, Gifford was a singer in a folk group, “Pennsylvania Next Right”, which performed frequently at school assemblies. After high school graduation in 1971, Gifford attended Oral Roberts University in Tulsa, Oklahoma, studying drama and music. During a summer in the early 1970s, she was a live-in secretary/babysitter for Anita Bryant at her home in Miami.

Kathie Lee married Paul Johnson, a Christian composer/arranger/producer/publisher, in 1976. They gained fame in Christian music, appearing on covers of Christian magazines. But the marriage was strenuous from the start and in 1981, Johnson moved out. The couple divorced in 1982.

Gifford’s career took off in the 1970s as a vocalist on the game show Name That Tune with Tom Kennedy. In 1978, she joined the cast of the short-lived Hee Haw spinoff, Hee Haw Honeys.

On June 24, 1985, Gifford replaced Ann Abernathy as co-host of The Morning Show on WABC-TV with Regis Philbin. The program went into national broadcast in 1988 as Live! with Regis and Kathie Lee, and Gifford became well known across the country. Throughout the 1990s, morning-TV viewers watched her descriptions of life at home with her sportscaster husband Frank, son Cody, and daughter Cassidy. Gifford left the show on July 28, 2000.

On October 18, 1986, Kathie Lee married a second time, this time to Frank Gifford, an American football player and television sports commentator. It was his third marriage after marriages with Maxine Avis Ewart and Astrid Lindley. With Ewart he had three children.

She appeared as a spokesperson for Slim Fast diet shakes after her son Cody was born. She also was the face of Carnival Cruise Lines in the late 1980s and early 1990s, singing “If my friends could see me now!” In 1991 she christened the Carnival Ecstasy, the 2nd of the Fantasy Class of cruise ships. In 1994, she appeared as herself in an episode of the NBC sitcom Seinfeld.

In 1996 the National Labor Committee, a human rights group, reported that sweatshop labor was being used to make clothes for the Kathie Lee line, sold at Wal-Mart. The group reported that a worker in Honduras smuggled a piece of clothing out of the factory, which had a Kathie Lee label on it. One of the workers, Wendy Diaz, came to the United States to testify about the conditions under which she worked. She commented, “I wish I could talk to [Kathie Lee]. If she’s good, she will help us.”

She did a number of voice overs most notably as Echidna in the 1998 TV series Hercules and in Higglytown Heroes as the Mail Carrier Hero in 2004.

In the late 1990s, Gifford began working in musical theatre. She contributed a number of musical numbers to Hats, and wrote and produced Under The Bridge, based upon the children’s book The Family Under The Bridge by Natalie Savage Carlson. In 2000 she released the album The Heart of a Woman on Universal.

In September 2005 she became a special correspondent on The Insider, a syndicated entertainment magazine television show, ending her relationship with that program upon her co-hosting role with Today.

She played the role of Miss Hannigan in a concert performance of Annie at Madison Square Garden in December 2006.

In 2007, she premiered Saving Aimee, a stage musical about evangelist Aimee McPherson, at the Signature Theatre in Arlington, Virginia. The premiere starred actress Carolee Carmello in the lead role. The show, now titled Scandalous: The Life and Trials of Aimee Semple McPherson, ran on Broadway from November 15, 2012, through December 9, 2012, with Carmello reprising her role as McPherson. On April 30, 2013, Carmello received her third Tony Award nomination for the performance.

On April 16, 2007, Gifford was a guest presenter at the Washington, D.C. Helen Hayes Award Ceremony, honoring contributions and professional accomplishments in theatre.

On March 31, 2008, NBC announced that Gifford was to join its morning show, Today, as co-host of the fourth hour titled Today with Kathie Lee and Hoda, alongside Hoda Kotb. This marked her return to morning television; in many markets, she aired directly after her old show, currently called Live with Kelly and Ryan. Because the fourth hour of Today airs live at 10:00 am ET, and Live with Kelly and Ryan airs live at 9:00 am ET, Gifford’s hour did not compete directly with her former show in most markets. Kotb and Gifford replaced Ann Curry and Natalie Morales. In the weeks prior to Gifford’s arrival, ratings indicated 1.9 million viewers of the fourth hour of Today. As of 2014, the fourth hour of Today with Gifford and Kotb has averaged 2.15 million total viewers, an increase of 13 percent over the 2008 ratings. On December 11, 2018, it was announced that she would be leaving Today in April 2019. Her final Today Show appearance was on April 5, 2019 with a party, including a video by her children Cody and Cassidy Gifford. In 2019, they won the Daytime Emmy Award for Outstanding Informative Talk Show Host.

In 2008, Gifford and David Friedman wrote a junior high school musical entitled Key Pin It Real. The play depicts a coming-of-age story about a young girl named Key Pin. The first production took place in December 2008 in Kendallville, Indiana, at East Noble High School.

She has written two autobiographical books, Just When I Thought I’d Dropped my Last Egg: Life and Other Calamities in 2010 and The Rock, the Road and the Rabbi to be released in early 2018. She has also written a number of children’s books.

She appeared as herself in the 2015 television film Sharknado 3: Oh Hell No!

Kathie Lee was 23 years younger than Frank. They had two children together, Cody Newton Gifford (born March 22, 1990) and Cassidy Erin Gifford (born August 2, 1993). They also shared a birthday: August 16. Frank died on August 9, 2015, from natural causes at their Greenwich, Connecticut, home at the age of 84. In 2017, she released “He Saw Jesus”, a very personal song Kathie Lee co-wrote (with songwriter Brett James) and dedicated to her husband. All proceeds from the song went to the international evangelical Christian humanitarian aid charity Samaritan’s Purse.

Gifford left Today in order to pursue a movie career both as an actress, and as a director and producer. In 2018 she filmed Then Came You in which she co-stars with Craig Ferguson. In 2018 she also filmed a Hallmark Christmas movie for Hallmark Movies & Mysteries called A Godwink Christmas. Gifford intends to make movies about the experiences of losing a loved one and being a widow, which she considers an underrepresented topic in Hollywood. Gifford has several projects in the works including sequels to Then Came You.