Thomas died around midnight at his home in Fort Lauderdale, Fla., from cancer of the liver. Thomas had a carcinoid tumor, which is a slow growing cancer, for more than a decade, the company said in a statement.
Thomas had quadruple heart bypass surgery in December 1996 and had gall-bladder surgery in July.
The founder and senior chairman of Wendy's International became a household face when he began pitching his burgers and fries in television commercials in 1989. The smiling Thomas, always wearing a white short-sleeved shirt and red tie, touted the virtues of fast-food in humorous ads.
"As long as it works, I'll continue to do the commercials," Thomas said in a 1991 interview. "When it's not working any longer, then I'm history."
"Dave was our patriarch, a great, big lovable man," said Jack Schuessler, chairman and CEO of Wendy's International, Inc., in the company statement. "He was the heart and soul of our company. He had a passion for great tasting hamburgers, and devoted his life to serving customers great food and helping those less fortunate in his community.
"Although Dave was widely popular, he was never very comfortable as a celebrity. He kept reminding us he was simply a hamburger cook," Schuessler said. "He was a humble man who was very comfortable in an apron behind a grill or in a business suit in a board room.
In an interview with CBS News Correspondent Sam Litzinger, Thomas once said he didn't think people could actually eat a "triple" the burger with three beef patties but they did. Thomas said he always tried to give good value.
But burgers were not his first love. Thomas, who was adopted as an infant, became a national advocate for adoption.
He created the Dave Thomas Foundation for Adoption, a not-for-profit organization focused on raising public awareness of adoption. The profits from his books, "Dave's Way" and "Well Done!" go to the foundation.
When the U.S. Postal Service issued a stamp for Adoption Awareness in 2000, Thomas appeared at events promoting the stamp all over the country.
He once testified before a congressional committee for a bill that would give a $5,000 tax credit to those who adopt children.
"I know firsthand how important it is for every child to have a home and loving family," he testified. "Without a family, I would not be where I am today."
Thomas, born July 2, 1932, was 12 when he got his first job delivering groceries in Knoxville, Tenn. He joined the restaurant business in the 1950s.
While working at a barbecue restaurant in Fort Wayne, Ind., he met KFC founder Col. Harland Sanders, who became a major influence in his life.
Thomas came to Columbus, Ohio in 1962 to take over four failing KFC restaurants for his boss, who promised Thomas a 45 percent stakin them if he turned them around. Sanders sold the restaurants back to KFC for $1.5 million in 1968, making Thomas a millionaire at 35.
He opened his first Wendy's Old Fashioned Hamburgers in Columbus a year later. He named the restaurant after his 8-year-old daughter Melinda Lou, nicknamed Wendy by her siblings.
The chain grew to 4,800 restaurants in the United States and 34 countries by 1996. That year, Wendy's acquired the 1,200-store, Canadian-based Tim Hortons chain of coffee and fresh-baked goods.
Thomas was a forgiving businessman.
The city of Philadelphia in 1994 wanted to fine Wendy's $98,400, claiming the restaurant was selling quarter-pounders that were short by up to a quarter of an ounce. The city later announced it made an error and withdrew the fine.
"I understand what happened," said Thomas, who visited the city shortly after the controversy. "Things happen. Mistakes happen. As far as we're concerned, we just want to go to the future. A bright future."
He tried to retire in 1982, but came back in 1989.
"They took the focus off the consumer," he said of the executives who took over the company.
In 1999 Thomas temporarily took charge of the company after the second death of its chief executive and president in less than four years. John Schuessler, formerly head of Wendy's U.S. operations, was appointed to those positions in 2000.
But it was the TV commercials that made Thomas famous. Industry analysts and company officials said the ads helped the company rebound from a difficult period in the mid-1980s when earnings sank.
"He's given Wendy's a corporate identity...a down-homey type image. The lack of sophistication is a real benefit for the company," one financial analyst said in 1991.
In 1996, Thomas filmed his 500th commercial. The company staged a lookalike contest that attracted 1,600 entrants vying for the grand prize: a chance to appear in a commercial with Thomas.
Thomas, who told the story of his life in "Dave's Way," told 2,500 Columbus public school seniors in 1993 the year he earned a high school equivalency certificate that his biggest mistake was not finishing high school.
"We have 4,000 restaurants today, but if I had gotten my high school diploma, we might have 8,000," he said.
©MMII CBS Worldwide Inc. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed. The Associated Press contributed to this report