The Wheeling & Lake Erie Railway connected Wheeling to Lake Erie at Toledo, opening the northeastern Ohio coalfields to both the Great Lakes and the Ohio River and offering Wheeling the best way to ship goods to Toledo, Chicago, Detroit, and Cleveland. In 1871, the W&LE was incorporated. Construction was slow because of the rugged terrain north of the Ohio River and the lack of financial resources. The enterprise owed its successful completion to investments by George Gould, the son of railroad tycoon Jay Gould. Building from the Toledo end, the line was eventually completed to Martins Ferry, Ohio, in 1891. From there, access to nearby Wheeling was provided by trackage rights on the Wheeling Bridge & Terminal Railway.

The W&LE prospered until the economic depression of the 1890s and a long strike by coal miners. The railroad entered a financial receivership in the late 1890s, and again with the collapse of the Gould empire in 1907. But the growth of the iron and steel industries of northeastern Ohio and the demand for their products in Detroit and Toledo, coupled with the demand for Ohio coal in the east, allowed the W&LE to recover and prosper. From 1920 to 1949, it did not fail to post a profit. In 1946 and 1947, the Nickel Plate Railroad purchased a majority of W&LE stock. The Wheeling & Lake Erie Railway was merged with the Nickel Plate into the Norfolk & Western Railway in 1964. In 1990 the corporate name was renewed when Norfolk Southern sold some of its holdings to a group of investors. The new W&LE is privately owned and handles over 135,000 carloads per year, operating in Ohio, Pennsylvania, West Virginia, and Maryland.