Greene built railroads in six states and designed municipal sewage and water systems for Washington, D.C., Detroit, and several other cities. In New York City, he designed the Croton Aqueduct reservoir in Central Park and the enlarged High Bridge over the Harlem River. He was one of twelve founders in New York City of the American Society of Civil Engineers and Architects. While on a trip to Maine for railroad surveying, he met Martha Barrett Dana, daughter of Samuel Dana, a prominent Massachusetts politician. They were married in Charlestown, Massachusetts, on February 21, 1837. They had six children together, including four sons (three of them later served in the military), one daughter, and one son who died in infancy.