Born in Bowling Green, Kentucky, Hines was a traveling salesman for a Chicago printer. By age 55 in 1935, Hines had eaten a lot of good and bad meals on the road, as part of his job, all across the country. At this time in the United States, there was no interstate highway system and only a few chain restaurants, except for in large, populated areas. Therefore, travelers depended on getting a good meal at a local restaurant.

Hines and his wife, Florence, began assembling a list for friends of several hundred good restaurants around the country. The list became so popular, that he began selling a paperback book entitled Adventures in Good Eating (1935), which highlighted restaurants and their featured dishes that Hines had personally enjoyed in cities and towns across America.

Hines was so successful, he added another book, recommending lodging for the night.

In 1952 Duncan Hines introduced Duncan Hines bread to the world through the Durkee's Bakery Company of Homer, New York. Principals Michael C. Antil Sr. and Albert Durkee, Lena Durkee, were the bakery proprietors. This was Duncan Hines' first foray into baked goods.

In 1953, Hines sold the right to use his name and the title of his book to Roy H. Park to form Hines-Park Foods, which licensed the name to a number of food-related businesses. The cake mix license was sold to Nebraska Consolidated Mills in Omaha, Nebraska, which developed and sold the first "Duncan Hines" cake mixes.

In 1957, Nebraska Consolidated Mills sold the cake mix business to the U.S. consumer products company, Procter & Gamble. The company expanded the business to the national market, and added a series of related products.

Also in 1957, Hines appeared as a guest challenger on the TV panel show To Tell The Truth.

Duncan Hines died of lung cancer on March 15, 1959.

The Duncan Hines brand is now owned by Pinnacle Foods. Hines is widely honored in his hometown of Bowling Green and a portion of U.S. Route 31W north of the city was named the Duncan Hines Highway after his death in 1959.

There is a museum showcasing Duncan Hines on the campus of Western Kentucky University in Bowling Green.

Duncan Hines was buried in Fairview Cemetery of Bowling Green, Kentucky, in the same series of Hines family plots as Thomas Hines.