Burke trained at the Culinary Institute of America, and soon thereafter traveled to France where he completed several stages with notable chefs such as Pierre Troisgros, Georges Blanc and Gaston Lenôtre. Burke's mastery of French culinary technique was confirmed when, at age 26, he won France's coveted Meilleurs Ouvriers de France Diplome d'Honneur for unparalleled skill and creativity with his native cuisine.

Burke returned to the U.S. as a sous chef for Wally Malouf at La Cremaillere and then for Charlie Palmer at The River Café, where he ascended to executive chef and earned three stars from The New York Times. In 1992, Burke opened the Park Avenue Café with Smith & Wollensky CEO Alan Stillman, and then, in 1996, he became vice president of culinary development for the Smith & Wollensky Restaurant Group.

Burke has been honored with Japan's Nippon Award of Excellence, the Robert Mondavi Award of Excellence and the CIA's August Escoffier Award. Nation's Restaurant News named Burke one of the 50 Top R&D Culinarians and Time Out New York honored him as the "Best Culinary Prankster" in 2003. In May 2009, Burke was inducted into the Who's Who of Food & Beverage in America by the James Beard Foundation. In that same month, he also won the distinctive Menu Masters award from Nation's Restaurant News , naming him one of the nation's most celebrated culinary innovators. In February 2012, Burke was honored by the culinary school at Johnson & Wales University with the Distinguished Visiting Chef Award, which is given to the world's most influential and celebrated chefs. In November 2012, he was named Restaurateur of the Year by the New Jersey Restaurant Association. In the same month, he was honored with a Concierge Choice Award, celebrating the best in New York City hospitality, winning the best chef award.

Chef Burke's vast talents have been showcased recently on television, including "Top Chef Masters," a guest spot on the "Every Day with Rachael Ray" show and as a mentor to Breckenridge Bourbon distiller Bryan Nolt on Bloomberg's small-business television series, "The Mentor".

In 2003, Burke teamed up with Donatella Arpaia to open davidburke & donatella (now known as David Burke Townhouse), of which he now has sole ownership. In 2005 came David Burke at Bloomingdale's, a dual-concept restaurant offering both a full service "Burke Bar Café" on one side and a "Burke in the Box" eat-in concept on the other. In 2006 Burke opened up David Burke's Primehouse in The James Hotel Chicago. His restaurant collection continued to grow that same year when he purchased Fromagerie, a fine dining restaurant in Rumson, New Jersey, where his culinary career began under founders Markus and Hubert Peter. His next ventures included David Burke Prime at Foxwoods Resort Casino in Connecticut and David Burke Fishtail in Manhattan, both of which opened in 2008. In February 2011, he opened David Burke Kitchen at The James Hotel New York in SoHo, bringing his signature whimsical style to downtown Manhattan.

During his tenure at The River Café, Burke began experimenting with interesting ingredients and cooking techniques. His first culinary innovations, including Pastrami Salmon™ (now available through Perona Farms), flavored oils and tuna tartare, revolutionized gastronomic technique. During his 12-year period at the Park Avenue Café, Burke created GourmetPops™, ready-to-serve cheesecake lollipops. Never one for slowing down, he continued to develop creative culinary products including easy Flavor-Transfer Spice Sheets and Flavor Sprays, both designed to eliminate fat while infusing flavor. His Can o' Cake concept, where cake is mixed, baked and eaten from a portable tin, is used throughout his restaurants. In 2011, Burke was honored to receive a United States patent, awarded to him for the process by which he uses pink Himalayan salt to dry-age his steaks for up to 75 days. Most recently, he teamed with 12NtM to create two non-alcoholic sparkling beverages, available in gourmet retailers such as Whole Foods and at his New York locations. Additionally, Burke is actively involved with culinology, an approach to food that blends the culinary arts and food technology. Burke also offers his consultant services to hotels, cruise lines and food experts.

Burke's first cookbook, Cooking with David Burke, was published in 1995, and his second, David Burke's New American Classics launched in April 2006.