Rudisill was born Edna Marie Faulk in Monroeville, Alabama. Her first marriage, to a Japanese man in the 1930s, ended in divorce due to her family's disapproval. She later wrote, "I really loved that man. He was so talented and such a sweet wonderful person. And I would have been happier with him than I was with the man I married after that." She married James Rudisill in 1939. She wrote, "A man who drinks excessively, it's not a happy marriage. We loved each other, but we had our times." The couple had one son, James, and Rudisill had three grandchildren.

Rudisill authored eight books, including Fruitcake: Memories of Truman Capote & Sook. She was a resident of Florida.

Rudisill's book Fruitcake (published by "Hill Street Press") led to her being invited to be a guest on The Tonight Show on December 14, 2000. During her first visit she showed Jay Leno and Mel Gibson how to make fruitcakes. This led to her being named the Fruitcake Lady and to several more appearances on The Tonight Show in which she instructed host Jay Leno and other guests in the preparation of various baked desserts.

In 2002, the "Ask the Fruitcake Lady" segments became a regular part of The Tonight Show. In these segments, viewers posed prerecorded questions to Rudisill (including questions of a graphic sexual nature), and her frank and often unpredictable responses were shown. In her responses she often lost patience with what she perceived as stupidity on the part of some questioners, and lapsed into profanity.

The following is an example of Rudisill's style of advice to Tonight Show viewers:

Viewer: My husband wants a new tool set for Christmas, but I know he won't use it and it'll just be a waste of money. What else can I give him that will make him happy?

Rudisill: Well, I should say it'd be to your benefit to give him sex. It'd be a lot cheaper for you to do that. I mean, why not? You -- I would, because even if you give him the other thing, then he's still going to come back for sex, you see. So just give him sex to begin with, and you don't have to buy the other thing. Go with the sex.

Marie Rudisill died in Hudson, Florida, on November 3, 2006, at the age of 95, just before the publication date of her latest book, Everything You Would Already Know If You Had Any Sense, on November 7. The November 8, 2006, broadcast of the Tonight Show included a tribute composed of highlights from her segments on the show, including one in which she cooked with (and was hugged and kissed on the cheek by) Tom Cruise.

An updated version of her 1989 cookbook, Sook's Cookbook: Memories and Traditional Recipes from the Deep South, was published by Louisiana State University Press in September 2008.