Bertram Grosvenor Goodhue was born on April 28, 1869, in Pomfret, Connecticut. Educated at Russell's Collegiate and Military Institute in New Haven from 1880-1883, where he was known among his classmates for skill in caricature and sketching. Without the financial means to attend college, Goodhue chose instead to seek an apprenticeship with an architectural firm in New York City. In 1884, he began as an assistant and novice draftsman in the office of Renwick, Aspinall and Russell, where he acquired an intensive, but largely self-directed, education in architectural design and production. Moonlighting after hours as a draftsman and designer, Goodhue became adept at highly detailed and atmospheric perspective renderings of extant structures and his own imaginative architecture.

In 1891, Goodhue was awarded a prestigious competition commission to design a cathedral in Dallas, Texas. Seeking collaborative assistance with this large project, Goodhue meet with Boston architects Ralph Adams Cram and Charles Francis Wentworth, who shortly offered him a full partnership in their firm. Although the cathedral remained unbuilt, Cram, Goodhue and Wentworth renamed Cram, Goodhue and Ferguson in 1898 received numerous commissions throughout the New England for ecclesiastical and civic buildings and residences in the English Gothic and Beaux-Arts styles. Both Goodhue and Cram were well known for associations and collaborations with noted artisans and craftsmen, particularly members of the Society of Arts and Crafts, Boston, with whom they frequently socialized. With the commission to design the United States Military Academy at West Point, New York, in 1902, Goodhue returned to New York City to open a branch of CGF to more closely supervise design and construction at the site. From that office, Goodhue designed numerous other major buildings, including St. Thomas Church (New York, New York, 1905-1920); Rice University (Houston, Texas, 1909); the Chapel of the Intercession (New York, New York, 1910-1914); and the Panama-California Exposition (San Diego, California, 1911-1915).

Goodhue's business relationship with Cram and Ferguson was dissolved in 1913 and Goodhue became an independent architect, employing several dozen staff by the start of World War I. He continued to receive significant commissions, including the Church of St. Vincent Ferrer (New York, New York, 191-1918); Saint Bartholomew's Church (New York, New York, 1914-1919); California Institute of Technology (Pasadena California, 1915-1917); Rockefeller Chapel at the University of Chicago (Chicago, Illinois, 1918-1928); the Nebraska State Capitol (Lincoln, Nebraska, 1920-1932); and the Los Angeles Public Library (1921-1926). Although never formally trained in architectural idioms, Goodhue's work frequently referred to the Arts and Crafts movement and a vernacular aesthetic, often incorporating the work of talented craftsmen.

Increasingly reductivist and modern after World War I, Goodhue often integrated historicist Mediterranean and Indo-European aesthetics with classical massing to achieve a recognizable style of his own. Goodhue's commissions took him across the United States, and he traveled widely for business and pleasure after 1900, often to see architecture of other cultures and regions, which he sketched with great aplomb. In the spring of 1924, after a trip to Los Angeles, where he was involved in building the public library, Goodhue succumbed to a heart attack, just days before his fifty-fifth birthday. His ashes were interred in a church of his own design, the Chapel of the Intercession, in New York City, in a tomb designed by a long-time colleague, sculptor Lee Lawrie. After Goodhue's sudden death, his office was reorganized as Bertram Grosvenor Goodhue Associates to complete outstanding commissions. In 1931 the firm was renamed by its partners Mayers, Murray & Phillip, closing finally in 1940.