She married James O'Rourke Killilea. They had five children: Marie, Kathryn Ann (who died in infancy), Karen Ann, James O'Rourke Jr. ("Rory"), and Kristin Rose. They also informally adopted Gloria Kyle, although this adoption was never finalized legally.

The family lived first in Rye, New York; later they moved to Larchmont, where they bought a house they christened "Sursum Corda" with the proceeds from Marie's first best-selling book.

Marie and James Killilea were devout Roman Catholics and raised their children accordingly.Killilea expressed her religious convictions in her writings.

She attended Mount St. Vincent Academy in Riverdale, New York and the Katharine Gibbs Business School.

In 1969, she was told by her doctors that she had a recurrence of lung cancer and had only three months to live. On referral, she went to Mercy Catholic Medical Center in Philadelphia for treatment by Dr. Isaac Djerassi. He prescribed huge doses of Methotrexate, a powerful drug, and in eight months, every trace of her cancer was reportedly eradicated.

Marie Killilea died in 1991, aged 78.

Marie Killilea wrote a biography of her daughter, called simply Karen, which became a best seller in 1952. It detailed Karen's struggle to overcome the limitations of her cerebral palsy and her family's fight to help her lead a satisfying life. A sequel, With Love From Karen, was published in 1963. The original was re-released in 1999. She also wrote a version of the story for children called "Wren".

• Karen, 1952 (re-released in 1999), New York: Buccaneer Books (ISBN 1-56849-098-4)

• With Love From Karen, (1963), New York: Buccaneer Books (ISBN 1-56849-099-2)
• Wren, (1981), New York: Dell Publishing Yearling Book (ISBN 978-0440797043)