In 1904, Goodhue built a townhouse at 106 East 74th Street, pushing the front to the building line and redesigning it in a mix of Gothic and Tudor styles.

His first was the Byzantine Revival style for St. Bartholomew's Episcopal Church on New York City's Park Avenue, built on a new platform just above the Grand Central Terminal railyards.

This was for the significant commission of the El Prado Quadrangle's layout and buildings at the major 1915 Panama–California Exposition, located in San Diego's Balboa Park.

[3][4][5] Goodhue and Gillespie had done a six-month research and acquisitions tour together through Egypt, Persia, and the Arabian Peninsula before collaborating on the classic Persian gardens layout and Roman and Spanish Colonial Revival residence at El Fureidis.

Towards the end of his career, he arrived at a highly personal style, a synthesis of simplified form and a generalized archaic quality, and those innovations paved the way for others to transition to modern architectural idioms.

Architectural sculptor Lee Lawrie created a Gothic styled tomb for him there, featuring Goodhue recumbent, crowned by a carved halo of some of his buildings.

After Goodhue's unexpected death in 1924, many of his designs and projects were brought to completion by architect Carleton Winslow Sr. in California, the successor firm of Mayers Murray & Phillip in New York, and other former associates.

Goodhue's offices had employed before they established their own independent practices and reputations, designers and architects such as Raymond Hood, Carleton Winslow Sr., Clarence Stein, and Wallace Harrison.

Thematic consultant Hartley Burr Alexander, Lee Lawrie, and Hildreth Meiere reassembled in the 1930s for the Rockefeller Center project collaboration with Raymond Hood.

[6] Along with Paul Cret and others, Goodhue is sometimes credited with being part of popularizing the art deco style in America, as in his design for the Nebraska State Capitol building, by which some may retroactively classify him as an early American Modernist.

However, his dedication to the integration of art and architecture was contrary to the spirit of Modernism design, and at least partly accounts for the academic and critical neglect of his work.