Couric married Jay Monahan in 1989. She gave birth to their first daughter, Elinor Tully "Ellie" Monahan, on July 23, 1991; their second daughter, Caroline "Carrie" Couric Monahan, was born on January 5, 1996. Jay Monahan died of colon cancer in 1998 at the age of 42; as a result, Couric is a spokeswoman for colon cancer awareness. She underwent a colonoscopy on-air in March 2000, and, according to a study published in 2003 in Archives of Internal Medicine, could have inspired many others to get checked as well:

Katie Couric's televised colon cancer awareness campaign was temporarily associated with an increase in colonoscopy use in 2 different data sets. This illustrates the possibility that a well-known individual can draw attention and support to worthwhile causes.

She also was very active in the National Hockey League's Hockey Fights Cancer campaign, appearing in some public service announcements and doing voice-overs for several others. Couric is currently a UNICEF Goodwill Ambassador for the United States.

On October 7, 2005, as part of National Breast Cancer Awareness Month, Couric broadcast her own mammogram on the Today show, in the hopes of recreating the "Couric Effect" around the issue of breast cancer.

Her sister Emily Couric, a Virginia Democratic state senator, died of pancreatic cancer at the age of 54 on October 18, 2001. Couric gave a eulogy at the funeral. She pointed out that it irritated Emily when people asked her if she was Katie Couric's sister. She told the mourners, "I just want you to know I will always be proud to say 'I am Emily Couric's sister'." Couric has two other siblings, Clara Couric Bachelor and John M. Couric Jr.

Couric was the honored guest at the 2004 Multiple Myeloma Research Foundation fall gala. As the Guest of Honor for the inaugural American Cancer Society Discovery Ball, Couric was recognized for her leadership in increasing cancer awareness and screening.

In 2011, Couric became the Honorary National Chair of the National Parkinson Foundation's Moving Day campaign, a grassroots campaign to spotlight Parkinson's disease awareness on a national level. Couric's father died in 2011 at age 90 from complications due to Parkinson's disease.

News sources have previously romantically linked Katie Couric to television sitcom producer Tom Werner. On December 13, 2011, Couric was reported to be splitting with her boyfriend of five years, financial executive Brooks Perlin, who is 17 years her junior.
During her tenure as the host of CBS Evening News, Couric received $15 million per year compensation.

In a September 2012 episode of Katie, Couric revealed that she had struggled with bulimia throughout college and for two years afterwards.