The LMRR's importance declined later in the 19th century, after three major railroads from the East built lines across the Allegheny Mountains and established east–west transportation systems through the state.
It continued independent operations until 1981, after being absorbed by Conrail during the period of extensive railroad restructuring in the late 20th century.
Other than trails, the main shipping route for the Great Lakes region to the rest of the nation to the east of the Allegheny Mountains suitable for trade was via the rivers leading to the Great Lakes and from there, to points east along the Erie Canal and south on the Hudson River to the major port of New York City.
Winter rendered transportation over the Alleghenies impracticable for large shipments, and the Erie Canal was subject to freezing.
The entire regions adjacent to the Great Lakes lacked waterway access to the Ohio River for shipment of their products.
The proposal that the two railroads would closely cooperate was projected to result in one of the major trade routes of the era, and of particular importance during winter months.
The road was completed to Springfield and inaugurated on August 10, 1846, bringing the total route-miles of its main line to 84 miles (135 km).
The Mad River and Lake Erie Railroad had encountered difficulties in raising capital, and construction was delayed for three years in reaching Springfield.
Revenues from local agricultural shipments were promising enough to enable the line to upgrade to heavier rails and make other improvements during the 1850s.
On February 23, 1870, the Little Miami Railroad leased in perpetuity, renewable forever, all of its assets, including the DX&B, the D&W, and the C&X, to the Pittsburgh, Cincinnati and St. Louis Railway, retroactive to December 1, 1869.
The system had cost $3,995,165 in track, right-of-way, and facilities, plus $1,065,968 in rolling stock, machinery, and a boat on the Ohio River.
The Lake Erie and Mad River Railroad, initially considered a company for a close relationship with the Little Miami, was absorbed into the competing New York Central system.
The Little Miami's most serious competitor, the Cincinnati, Hamilton and Dayton Railway (1895–1917), became part of the competitive Baltimore and Ohio system.
In the mid-20th century, there was extensive railroad restructuring following changes in the industry, which had been affected by the expansion of trucking and use of passenger automobiles following construction of the interstate highway system.
Together with the Ohio Department of Natural Resources (ODNR), the local governments of Xenia and Yellow Springs purchased parts of the abandoned right of way from 1973 to 1983.