Darlene married Robert Cates, a U.S. Marine, on January 11, 1963. She had one daughter, Sheri Ann (b. 1966), and two sons, Mark (b. 1967) and Chris (b. 1971). She had four grandchildren and lived in the Dallas suburbs. In 1992, she received her high school diploma via correspondence courses. In 2012, Cates had lost 240 pounds after a series of 2010 health issues kept her hospitalized for nearly a year, and she expressed a Desire to resume her acting career.

Cates was born in Borger, Texas to Truman Madison and Dorothy Ann Guthrie, and grew up in Dumas. Her parents divorced when she was 12 years old. She took solace in food, and her overeating led to obesity. She underwent gastroplasty in 1981, when she weighed 408 lb (29 st 2 lb or 185 kg). She lost 99 lb (7 st 1 lb or 45 kg) but eventually gained the weight back and more, topping out at 548 lb (39 st 2 lb or 249 kg).

Author and Screenwriter Peter Hedges saw a tape of Cates on a 1992 episode of Sally entitled "Too Heavy to Leave Their House". On the show, she discussed her battle with obesity and how it had affected her life. In 1986, pelvic infections caused by her excess weight kept her bedridden for two years, during which she gained an additional 149 pounds. Hedges offered her the role of a morbidly obese mother in the 1993 film What's Eating Gilbert Grape, which she accepted. Television roles followed on the shows Picket Fences in 1994 and Touched by an Angel in 1996. She had a small role in the 2001 film Wolf Girl. Producer J. Miles Dale flew a small crew and the film's stars from Romania to Texas to shoot their scenes with Cates.

Darlene died in her sleep at age 69 on March 26, 2017. Her daughter, Sheri Cates Morgan, announced her passing on a Facebook post.