He designed Canberra, Australia's capital city, the New South Wales towns of Griffith and Leeton, and (with his wife) the Sydney suburb of Castlecrag.

[1] The University of Illinois program was run by Nathan Clifford Ricker, a German-educated architect, who emphasized the technical aspects of architecture.

After his studies, Griffin moved to Chicago and was employed as a draftsman for two years in the offices of progressive architects Dwight H. Perkins, Robert C. Spencer, Jr., and H. Webster Tomlinson in "Steinway Hall".

This style is marked by horizontal lines, flat roofs with broad overhanging eaves, solid construction, craftsmanship, and strict discipline in the use of ornament.

Louis Sullivan was influential among Prairie School architects and Griffin was an admirer of his work, and of his philosophy of architecture which stressed that design should be free of historical precedent.

With seven of these houses being located on West 104th Place—comprising the largest concentration of original prairie style homes built in Chicago—the street as it runs between Hale Avenue on the west to Prospect Avenue on the east was designated the Griffin Place Historic District, which comprises a part of the larger Ridge Historic District.

[1] On June 29, 1911, Griffin married Marion Lucy Mahony, a graduate of the Massachusetts Institute of Technology in architecture.

[2] A housing development with several homes designed by Griffin and Mahony, Rock Crest – Rock Glen in Mason City, Iowa, is seen as their most dramatic American design development of the decade and remains the largest collection of Prairie Style homes surrounding a natural setting.

[3] From 1899 to 1914, Griffin created more than 130 designs in his Chicago office for buildings, urban plans and landscapes; half of these were built in the mid-western states of Illinois, Iowa, Michigan and Wisconsin.

[4] In April 1911, the Australian Commonwealth Government held an international competition to produce a design for its new, as yet unnamed, federal capital city.

The Griffins joined the Naturalists Society of New South Wales in 1914, where they enjoyed organized bush walks and field studies.

At the same time he was negotiating a three-year contract with the Commonwealth Government to remain in Australia and oversee the implementation of his plan, which he felt had already been compromised.

[1] In this role, Griffin oversaw the design of North and South Canberra, though he struggled with considerable political and bureaucratic obstacles.

In 1917, a Royal Commission determined that they had undermined Griffin's authority by supplying him with false data which he had used to carry out his work.

The Commonwealth Government under the leadership of Prime Minister Hughes had removed Griffin as Director of Design and Construction after disagreements over his supervisory role, and in 1921 it created the Federal Capital Advisory Committee, with John Sulman as chair.

The grave of General Bridges on Mount Pleasant[11] was the only permanent structure designed by him to be built in Canberra.

[12] The Griffins' office in Chicago closed in 1917; however, they had successful practices in Melbourne and Sydney, which were a strong motivation for their continuing to live in Australia.

[13] While supervising activities in Canberra, Griffin spent much time in Melbourne and, in 1918, became a founder, with Royden Powell, of the Henry George Club, an organization devoted to providing a home for the Single Tax movement.

[14] The Griffins' first major commission after leaving Canberra was the Capitol Theatre in Melbourne; it opened on November 7, 1924.

The GSDA's goal was the development of an idyllic community with a consistent architectural feel and bushland setting.

Almost all the houses Griffin designed in Castlecrag were small and had flat roofs, and he included an internal courtyard in many of them.

Having won one international competition, as architects who were both well acquainted with Chicago and recognized as practical visionaries, they offered a solution that was positive, forward-looking and elegant.

It anticipated, and would have been a near neighbor of, Chicago's 333 North Michigan by Holabird & Roche (1928); with stylistic echos in John and Donald Parkinson's Bullocks Wilshire, in Los Angeles (1929), as well as Adah Robinson and Bruce Goff's Boston Avenue Methodist Church, Tulsa (1929).

It has been listed by the National Trust of Australia and the Royal Australian Institute of Architects as a building of significance.

Although he had planned to stay in India only to complete the drawings for the library, he soon received more than 40 commissions, including the University of Lucknow Student Union building; a museum and library for the Raja of Mahmudabad; a zenana (women's quarters) for the Raja of Jahangirabad; Pioneer Press building, a bank, municipal offices, many private houses, and a memorial to King George V. He also won complete design responsibility for the 1936–1937 United Provinces Exhibition of Industry and Agriculture.

His 53 projects for the 160-acre (0.65 km2) site featured a stadium, arena, mosque, imambara, art gallery, restaurant, bazaar, pavilions, rotundas, arcades, and towers,[25][26] however, only part of his elaborate plans were fully executed.

[28] While in India, Griffin also published numerous articles for the Pioneer, writing about architecture, in particular about ventilation design improvements.

She closed down their Indian offices before leaving their Australian practice in the hands of Griffin's partner, Eric Milton Nicholls, and returned to Chicago.