Burnham was not a good student but he was good at drawing. He moved to the eastern part of the country at the age of 18 to be taught by private tutors in order to pass the admissions examinations for Harvard and Yale, failing both apparently because of a bad case of test anxiety. In 1867, when he was 21 he returned to Chicago and took an apprenticeship as a draftsman under William LeBaron Jenney of the architectural firm Loring & Jenney. Architecture seemed to be the calling he was looking for, and he told his parents that he wanted to become “the greatest architect in the city or country”.

Nevertheless, the young Burnham still had a streak of wanderlust in him, and in 1869 he left his apprenticeship to go to Nevada with friends to try mining gold, at which he failed. He then ran for the Nevada state legislature and failed to be elected. Broke, he returned again to Chicago and took a position with the architect L. G. Laurean. When the Great Chicago Fire hit the city in October 1871, it seemed as if there would be endless work for architects, but Burnham chose to strike out again, becoming first a salesman of plate glass windows, then a druggist. He failed at the first and quit the second. He later remarked on “a family tendency to get tired of doing the same thing for very long”.

At age 26, Burnham moved on to the Chicago offices of Carter, Drake and Wight where he met future business partner John Wellborn Root, who was 21 and four years younger than Burnham. The two became friends and then opened an architectural office together in 1873. Unlike his previous ventures, Burnham stuck to this one. Burnham and Root went on to become a very successful firm. Their first major commission came from John B. Sherman, the superintendent of the massive Union Stock Yards in Chicago, which provided the liveliehood – directly or indirectly – for one-fifth of the city’s population. Sherman hired the firm to build for him a mansion on Prairie Avenue at Twenty-first Street among the mansions of Chicago’s other merchant barons. Root made the initial design. Burnham refined it and supervised the construction. It was on the construction site that he met Sherman’s daughter, Margaret, whom Burnham would marry in 1876 after a short courtship. Sherman would commission other projects from Burnham and Root, including the Stone Gate, an entry portal to the stockyards which became a Chicago landmark.

Burnham married Margaret Sherman, the daughter of his first major client, John B. Sherman, on January 20, 1876. They first met on the construction site of her father’s house. Her father had a house built for the couple to live in. During their courtship, there was a scandal in which Burnham’s older brother was accused of having forged checks. Burnham immediately went to John Sherman and offered to break the engagement as a matter of honor but Sherman rejected the offer, saying “There is a black sheep in every family.” However, Sherman remained wary of his son-in-law, who he thought drank too much.

In 1881, the firm was commissioned to build the Montauk Building which would be the tallest building in Chicago at the time. To solve the problem of the city’s water-saturated sandy soil and bedrock 125 feet (38 m) below the surface, Root came up with a plan to dig down to a “hardpan” layer of clay on which was laid a 2-foot (0.61 m) thick pad of concrete overlaid with steel rails placed at right-angles to form a lattice “grill”, which was then filled with Portland cement. This “floating foundation” was, in effect, artificially-created bedrock on which the building could be constructed. The completed building was so tall compared to existing buildings that it defied easy description, and the name “skyscraper” was coined to describe it. Thomas Talmadge, an architect and architectural critic said of the building, “What Chartres was to the Gothic cathedral, the Montauk Block was to the high commercial building.”

Although the firm was extremely successful, there were several notable setbacks. One of their designs, the Grannis Block in which their office was located, burned down in 1885 necessitating a move to the top floor of The Rookery, another of their designs. Then, in 1888, a Kansas City, Missouri, hotel they had designed collapsed during construction, killing one man and injuring several others. At the coroner’s inquest, the building’s design came in for criticism. The negative publicity shook and depressed Burnham. Then in a further setback, Burnham and Root also failed to win the commission for design of the giant Auditorium Building, which went instead to their rivals, Adler & Sullivan.

Burnham and Margaret remained married for the rest of his life. They had five children, two daughters and three sons, including Daniel Burnham Jr. born in February 1886, who became an architect and urban planner like his father. He worked in his father’s firm until 1917, and served as the Director of Public Works for the 1933-34 Chicago World’s Fair, known as the “Century of Progress”.

The talents of the two partners were complementary. Both men were artists and gifted architects, but Root had a knack for conceiving elegant designs and was able to see almost at once the totality of the necessary structure. Burnham, on the other hand, excelled at bringing in clients and supervising the building of Root’s designs. They each appreciated the value of the other to the firm. Burnham also took steps to ensure their employees were happy: he installed a gym in the office, gave fencing lessons and let employees play handball at lunch time. Root, a pianist and organist, gave piano recitals in the office on a rented piano. Paul Starrett, who joined the office in 1888 said “The office was full of a rush of work, but the spirit of the place was delightfully free and easy and human in comparison to other offices I had worked in.”

On January 15, 1891, while the firm was deep in meetings for the design of the World’s Columbian Exposition, Root died after a three-day course of pneumonia. As Root had been only 41 years old, his death stunned both Burnham and Chicago society. After Root’s death, the firm of Burnham and Root, which had had tremendous success producing modern buildings as part of the Chicago School of architecture, was renamed D.H. Burnham & Company. After that the firm continued it successes and Burnham extended his reach into city design.

In addition, the Reliance Building in Chicago which was designed by Burnham and Root, is now the Hotel Burnham, although Root was the primary architect before his death in 1891.

In 1901, Burnham designed the Flatiron Building in New York City, a trailblazing structure that utilized an internal steel skeleton to provide structural integrity; the exterior masonry walls were not load-bearing. This allowed the building to rise to 22 stories. The design was that of a vertical Renaissance palazzo with Beaux-Arts styling, divided like a classical column, into base, shaft and capital.

Initiated in 1906 and published in 1909, Burnham and his co-author Edward H. Bennett prepared a Plan of Chicago which laid out plans for the future of the city. It was the first comprehensive plan for the controlled growth of an American city and an outgrowth of the City Beautiful movement. The plan included ambitious proposals for the lakefront and river. It also asserted that every citizen should be within walking distance of a park. Sponsored by the Commercial Club of Chicago, Burnham donated his services in hopes of furthering his own cause.

Burnham’s city planning projects did not stop at Chicago though. Burnham had previously contributed to plans for cities such as Cleveland (the 1903 Group Plan), San Francisco (1905),Manila (1905,) and Baguio in the Philippines, details of which appear in the 1909 Plan of Chicago publication. His plans for the redesign of San Francisco were delivered to the Board of Supervisors in September 1905, but in the haste to rebuild the city after the 1906 earthquake and fires Burnham’s plans were ultimately ignored. In the Philippines, Burnham’s Plan for Manila never materialized due to the outbreak of World War II and the relocation of the capital to another city after the war. Some components of the plan, however, did come into fruition including the shore road which became Dewey Boulevard (now known as Roxas Boulevard) and the various neoclassical government buildings around Luneta Park, which very much resemble a miniature version of Washington, D.C., in their arrangement.

When Burnham was in his fifties, his health began to decline. He developed colitis and in 1909 was diagnosed with diabetes, which affected his circulatory system and led to an infection in his foot which was to continue for the remainder of his life.

In Washington, D.C., Burnham did much to shape the 1901 McMillan Plan which led to the completion of the overall design of the National Mall. The Senate Park Commission, or McMillan Commission established by Michigan Senator James McMillan, brought together Burnham and three of his colleagues from the World’s Columbian Exposition: architect Charles Follen McKim, landscape architect Frederick Law Olmsted Jr., and sculptor Augustus Saint-Gaudens. Going well beyond Pierre L’Enfant’s original vision for the city, the plan provided for the extension of the Mall beyond the Washington Monument to a new Lincoln Memorial and a “pantheon” that eventually materialized as the Jefferson Memorial. This plan involved significant reclamation of land from swamp and the Potomac River and the relocation of an existing railroad station, which was replaced by Burnham’s design for Union Station. As a result of his service on the McMillan Commission, in 1910 Burnham was appointed a member and first chairman of the United States Commission of Fine Arts helping to ensure implementation of the McMillan Plan’s vision. Burnham served on the commission until his death in 1912.

On April 14, 1912, Burnham and his wife were aboard the S.S. Olympic of the White Star Line, traveling to Europe to tour Heidelberg, Germany. When he attempted to send a telegram to his friend Frank Millet who was traveling the opposite direction, from Europe to the United States, on the S.S. Titanic, he learned that the ship had sunk in an accident and Millet did not survive. Burnham died only 47 days later from colitis complicated by his diabetes and food poisoning from a meal eaten in Heidelberg.

In his career after the fair, Burnham became one of the country’s most prominent advocates for the Beaux-Arts movement as well as the revival of Neo-classical architecture which began with the fair. Much of Burhham’s work was based on the classical style of Greece and Rome. In his 1924 autobiography, Louis Sullivan, one of the leading architects of the Chicago School, but one who had a difficult relationship with Burnham over an extended period of time, criticized Burnham for what Sullivan viewed as his lack of original expression and dependence on classicism. Sullivan went on to claim that “the damage wrought by the World’s Fair will last for half a century from its date, if not longer” – a sentiment edged with bitterness, as corporate America of the early 20th century had demonstrated a strong preference for Burnham’s architectural style over Sullivan’s.

Burnham and Root went on to build more of the first American skyscrapers, such as the Masonic Temple Building in Chicago. Measuring 21 stories and 302 feet, the temple held claims as the tallest building of its time, but was torn down in 1939.

Tributes to Burnham include Burnham Park and Daniel Burnham Court in Chicago, Burnham Park in Baguio City in the Philippines, Daniel Burnham Court in San Francisco (formerly Hemlock Street between Van Ness Avenue and Franklin Street), the annual Daniel Burnham Award for a Comprehensive Plan (run by the American Planning Association), and the Burnham Memorial Competition which was held in 2009 to create a memorial to Burnham and his Plan of Chicago. Collections of Burnham’s personal and professional papers, photographs, and other archival materials are held by the Ryerson & Burnham Libraries at the Art Institute of Chicago.