His innovations in wooden bridges and curved masonry viaduct designs significantly advanced American civil engineering in the 19th century.

His engineering survey plans for crossing the Allegheny Mountains were later incorporated into legislation guiding the construction of the Pacific railroads, establishing his lasting impact on national infrastructure.

Their eldest son, Charles Hazelhurst Latrobe (1833–1902), moved to Florida, where he married and later joined the Confederate States Army.

[2] Through his brother's influence, Latrobe was hired as a rodman on the survey locating the railroad west of Ellicott's Mills.

But, in 1829, the Chesapeake and Ohio Canal Company obtained two legal injunctions that "...restrain(ed) the (railroad) from constructing the road at all, within the limits of Frederick County."

[8]: 159–168  Nicknamed "Latrobe's Folly" by those who doubted the massive structure could support itself, the bridge remains in use today (as of 2024), carrying far heavier loads than ever envisioned.

[8] In 1838, Latrobe completed reconnaissance and surveys to extend the Main Stem of the Baltimore and Ohio railroad from Harper's Ferry to Wheeling and Pittsburgh.

[16] Miller later ascribed the failure to the difficulties of assembling members due to available means for traveling in the country at the time.

[16] One of the other difficulties members would have to contend with was the requirement to produce each year one previously unpublished paper or "...present a scientific book, map, plan or model, not already in the possession of the Society, under the penalty of $10.

In 1842, Latrobe became chief engineer of the Baltimore and Ohio railroad, serving for 22 years [7][12]: 54  and was appointed to the concurrent position of general superintendent of the road in 1847.

[2] Pallbearers included fellow engineers Charles P. Manning, chief engineer for the Baltimore City water works, General William Price Craighill, Future president of the American Society of Civil Engineers-Mendes Cohen,Richard McSherry, Cary Breckinridge Gamble.

"[2] The eulogy noted that the commercial prosperity of Baltimore, the "... tunneled hills and long lines of railroads were monuments to that success and would live longer than marble or granite.

[22] His brother John H. B. Latrobe was on the cemetery's board of directors as well as helped found the Maryland Historical Society, which maintains the family papers.

[23] Latrobe played a prominent role in the construction of the Baltimore and Ohio railroad, particularly the location of the road in one of the first crossings of the Alleghenies.