Such formal education as Goodhue had was acquired at Russell's Collegiate and Commercial Institute, New Haven, Connecticut. In 1882 he became an office boy in the New York architectural firm of Renwick, Aspinwall and Russell; within two years he was the firm's chief draughtsman, largely due to James Renwick's tutelage. In 1891, well steeped in the Gothic revival styles favored by Renwick and with a commission to build a cathedral in Dallas, Texas, Goodhue joined Ralph Adams Cram's firm in Boston, and by the mid-1890s was his full partner. Cram was the most noted champion of the Gothic style in architecture of his time. The firm name became Cram, Goodhue and Ferguson in 1899.
When in 1903 the partnership received the commission to expand the United States Military Academy at West Point Goodhue set up a branch office in New York. Goodhue's interest began to expand to other more progressive architectural modes, leading to tensions with Cram, and the partnership was dissolved in 1913. The last major building on which they worked cooperatively was St. Thomas's Church in New York.
An admirer of Spanish Colonial architecture, Goodhue, as supervising architect, employed this style in the buildings of the San Diego Panama-Pacific Exposition of 1915. His work there was influential in the widespread revival style. However, his conceptions were not limited in their historical and decorative associations. The facade of St. Bartholmew's Church, 1910, and the Grolier Club, both in New York; the Nebraska State Capitol, 1916-1921, in Lincoln; and the National Academy of Science, 1924, in Washington, D. C. are among his most well-known designs.
One of Goodhue's special interests was typography and fine book design. He originated several type fonts, including Cheltenham, and was a leader in the revival of fine printing in America.
On his death the Academy noted: "American architecture sustains the kind of loss which, while intrinsically great, is made to seem greater by the suggestion of unfulfilled potentialities."
