She is the daughter of James "Jimmy" and Virginia "Genny" Whelchel. Her parents divorced in 1981 and her mother married Roy Coleman in 1983. Lisa was raised for most of her childhood in Fort Worth, Texas and she was in the class of 1980 at Liberty Christian Academy in Argyle, Texas.

At age 12, Whelchel was recruited in Texas by talent scouts who were looking for children interested in working with Disney Studios as a Mouseketeer on The New Mickey Mouse Club. She moved to California the next year and appeared on the show in syndication from 1977 to 1978.

As a cast member of The Facts of Life, Whelchel once refused a storyline that would have made her character the first among the four main young women on the show to lose her virginity. Having become a Christian when she was ten years old, Whelchel refused because of her Christian convictions, and the storyline was rewritten for the character of "Natalie," portrayed by Mindy Cohn. Whelchel appeared in every episode of the series except that one.

Today, Lisa is a homeschooling mother, speaker, and pastor's wife. She is the bestselling author of So You're Thinking About Homeschooling, The Facts of Life (and Other Lessons My Father Taught Me), and the Gold Medallion nominee Creative Correction. Lisa and her husband, pastor Steve Cauble, live in Texas with their children Tucker, Haven, and Clancy.