She was born Kathleen Marie Babineaux in New Iberia, Louisiana, the daughter of Louis Babineaux and his wife, the former Lucille Fremin, both of Cajun ancestry. Her Babineaux grandfather was a farmer and grocer with a country store, and her father was a small businessman who moved to the rural hamlet of Coteau, a community near New Iberia with one church and one elementary school. Blanco attended Mount Carmel Academy, an all-girls school run by the Roman Catholic Sisters of Mount Carmel, which was situated on the banks of Bayou Teche. In 1964, Blanco received a Bachelor of Science in Business Education from the University of Louisiana at Lafayette, then named the University of Southwestern Louisiana. She was also a member of Kappa Delta sorority. On August 8, 1964, she married Raymond Blanco, a football coach and educator; the couple had four daughters: Karmen, Monique, Nicole, and Pilar and two sons: Ray Jr., and Ben.

Prior to her election as governor, Blanco served twenty years in public office. In 1983, elected as the first woman legislator from the city of Lafayette, she served five years in the Louisiana House of Representatives. In her first term, she and her friend Evelyn Blackmon of West Monroe were two of only five women in both houses of the legislature. Blanco in 1988 defeated the Republican Kernan “Skip” Hand to become the first woman in Louisiana elected to the Louisiana Public Service Commission, a post that she held for seven years, She was also the first woman chairman of the PSC. She was then elected Lieutenant Governor, a post that she held for eight years.

Blanco was elected on November 15, 2003, defeating her Republican opponent Bobby Jindal in the general election, by a margin of 52 to 48 percent. On January 12, 2004, she took the oath of office in both English and French languages, succeeding Murphy J. Foster Jr. She retained Foster’s chief of staff Andy Kopplin. She named as the new state commissioner of administration Jerry Luke LeBlanc, who had succeeded her in the state House in 1989 when she became a public service commissioner. Blanco traveled more than her predecessor, seeking new sources of economic development for the state. She visited Nova Scotia and in December 2004 visited Cuba to boost its trade with the state. During this controversial visit, she met with President Fidel Castro, with whom the United States government had no formal diplomatic relations. In 2005, Blanco also visited the Asian countries of Japan, China, and Taiwan.

On August 27, 2005, Blanco, speaking about Hurricane Katrina, told the media in Jefferson Parish, “I believe we are prepared. That’s the one thing that I’ve always been able to brag about.” Later that day, she issued a request for federal assistance and USD $9 million in aid to U.S. President George W. Bush, which stated,

Also in the request letter, the governor stated: “In response to the situation, I have taken appropriate action under State law and directed the execution of the State Emergency Plan on August 26, 2005 in accordance with Section 501 (a) of the Stafford Act. A State of Emergency has been issued for the State in order to support the evacuations of the coastal areas in accordance with our State Evacuation Plan.”

On September 1, 2005, with reports of looting and lawlessness escalating, Blanco announced she was sending 300 Louisiana National Guardsmen to supplement the New Orleans Police Department, saying,

President Bush, during a visit to Louisiana on September 2, 2005, five days after the storm, offered to federalize the Louisiana National Guard to simplify the command structure. The Governor declined, because the Guard would then become part of the federal military forces and therefore lose much-needed policing powers. The President subsequently continued to press the offer, so Blanco rejected it in writing, citing the need for flexibility in National Guard operations, particularly the need for the Guard in areas other than New Orleans where the military was not currently operating. Governor Haley Barbour of Mississippi reportedly declined a similar offer from the President. Had either state’s National Guard been federalized, they would not have been able to directly enforce state law (i.e. control looting) under the provisions of the 1878 Posse Comitatus Act. It had not previously been a policy during natural disasters to combine the command of National Guard and military operations under the authority of the President. President Bush had the power to take command of a state’s National Guard units under the Insurrection Act of 1807 without the agreement of a state Governor, but no President had done this since Lyndon Johnson in the 1960s and President Bush had so far also declined to do so. However, Blanco and Major General Bennett Landreneau, Louisiana Adjutant General and senior Louisiana National Guard officer, co-operated closely with U.S. Army Lieutenant General Honoré, who was then commanding Federal military operations under Joint Task Force Katrina.

On September 14, after President Bush had accepted responsibility for all problems that occurred at the federal level, Blanco accepted responsibility for all problems that occurred at the state level. Blanco stated, “At the state level, we must take a careful look at what went wrong and make sure it never happens again. The buck stops here, and as your governor, I take full responsibility.” In 2006, a Congressional report stated that the “National Response Plan did not adequately provide a way for federal assets to quickly supplement or, if necessary, supplant first responders.”

Early in 2006, Blanco was inducted into the Louisiana Political Museum and Hall of Fame in Winnfield.

On June 19, 2006, Blanco announced that she would send the National Guard to patrol the streets of New Orleans after five teenagers were killed, in an effort to combat a greatly increased rate of violent crime.

Also on June 19, 2006, Blanco signed into law a ban on most forms of abortion (unless the life of the mother was in danger or her health would be permanently damaged) once it passed the state legislature. Although she felt exclusions for rape or incest would have “been reasonable,” she felt she should not veto based on those reasons. The bill would only go into effect if the United States Supreme Court reversed Roe v. Wade.

In August 2006, Blanco filed a lawsuit and formally objected to the federal Gulf of Mexico lease sale “to force the federal government to spend part of its oil and gas income from the Outer Continental Shelf to help shore up Louisiana’s coastline”.

In December 2006, Blanco called a special session of the Louisiana State Legislature which she intended to use to dispense $2.1 billion worth of tax cuts, teacher raises, road projects and other spending programs. Legislators allied with Blanco attempted to lift a spending cap imposed by the Constitution of Louisiana, but Republican lawmakers rejected the governor’s spending measure. The high-profile defeat further eroded Blanco’s political reputation.

By late 2006 and early 2007, Blanco was facing increasingly heated accusations of delays in administering the Road Home Program, a state-run program which Blanco and the Louisiana Recovery Authority had set up following Katrina in order to distribute federal aid money to Katrina victims for damage to their homes. By January 2007, fewer than 250 of an estimated 100,000 applicants had received payments from the program, and many of the payments were apparently based on assessments which grossly undervalued the cost of damage to homes.

Facing an upcoming re-election campaign with greatly reduced popularity, Blanco made repeated public criticisms of the administration of President Bush in January 2007. Noting that Bush neglected to mention Gulf Coast reconstruction in his 2007 State of the Union Address, Blanco called for a bipartisan Congressional investigation into the conduct of the Bush administration following Katrina, to determine whether partisan politics played a role in the slow response to the storm. This call followed comments by former Federal Emergency Management Agency (FEMA) director Michael D. Brown, who claimed that the White House offer to federalize the National Guard in the days following the storm was part of a plan to upstage Blanco. Blanco has also publicly stated that Mississippi received preferential treatment because its governor, Haley Barbour, is Republican.

Blanco announced on March 20, 2007 that she would not seek re-election. On January 14, 2008, Bobby Jindal succeeded her as governor.

In December 2017, Blanco was diagnosed with ocular melanoma metastatic to her liver. A year later at a meeting of the civic association, the Council for a Better Louisiana, Blanco said there is “no escape” from the disease as it had metastasized throughout her body and she has “made peace” with her future. On April 19, 2019, it was announced that she was in hospice care.

Blanco died on August 18, 2019, at the St. Joseph Hospice Carpenter House in Lafayette, Louisiana.