He was sent to Germany to complete his education at the University of Leipzig, and served a term in the Prussian Army before returning to his native country in 1785. At the age of twenty-three Latrobe went to London to study architecture under the late Samuel Pepys Cockerell, a pioneer in the Greek Revival
In December, 1798 Mr. Latrobe settled in Philadelphia, and opening an office for architectural practice, launched a career that was to bring him renown. He won recognition in designing a building for the Bank of Pennsylvania, notable as the first public structure of Greek Revival design to be built in the U. S. Later he designed the United States Bank, completed after he died by W. Strickland, now the old Custom House. Other works in Philadelphia credited to him were the Water Works Building, on site of the present City Hall; original building of the Fine Arts Academy built in 1804 at the corner of Chestnut and 10th Street, remodelling and enlargement of the building intended to be for occupancy of the president of the University of Pennsylvania, 1804; and addition of a wing to the Chestnut Street Theatre. In addition Latrobe designed "Sedgley", a country house near Philadelphia for William Gramont believed to have been the first Gothic residence in the city , and at Carlisle, Pa, the original unit of Dickinson University.
Meantime at the U. S. Capitol at Washington, the north wing (old Senate Chamber, later the Supreme Court Room) had been completed under William Thornton, and foundation laid for the south wing (old House of Representatives, now Statuary Hall). In 1804 President Jefferson appointed Latrobe to the post of "Surveyor of Buildings", in charge of public buildings, and altho his ideas were in conflict with Thornton’s own work at the Capitol, their differences were eventually smoothed out and the south wing brought to completion under Latrobe’s direction. He is also said to have designed the colon-naded terraces at the “President’s House," and in 1807 prepared a plan for remodelling the house itself. After the British attack in 1814 during which the Capitol suffered considerable damage, Latrobe was recalled to Washington to supervise its reconstruction, and continued in charge of the work over a period of three years.
In private practice he designed two churches in Washington, St. John’s Episcopal, dating from 1817 (restored in 1917), and Christ Church on Street near Sixth, S. E., a Gothic edifice later much altered. Also credited to this architect is the Stephen Decatur house at 748 Jackson Place N. W., Washington, and other distinctive residences in the South.
In Baltimore the Roman Catholic Cathedral of the Assumption of the Blessed Mary, the first Catholic Cathedral in the U. S. built between 1806 and 1821, was one of Mr. Latrobe’s outstanding achievements, and interesting as one of the earliest churches designed in the Greek Revival rather than the traditional Colonial” style. The present portico was a later addition of 1864. His last important work, completed shortly before his decease was the Louisiana State Bank at New Orleans, a brick and stucco building with wrought iron balconies, later much altered
While in Philadelphia, Latrobe married Mary Elizabeth Hazlehurst (1771–1841), in 1800. The couple had several children together.