In October 1867, the Cleveland, Painesville and Ashtabula Railroad leased the Cleveland and Toledo Railroad. The CP&A changed its name to the Lake Shore Railway on March 31, 1868, and on February 11, 1869, the Lake Shore absorbed the Cleveland and Toledo. On April 6 the Michigan Southern and Northern Indiana Railroad and Lake Shore merged to form the Lake Shore and Michigan Southern Railway, which absorbed the Buffalo and Erie Railroad on June 22, giving one company the whole route from Buffalo to Chicago.
Around 1877, Cornelius Vanderbilt and his New York Central and Hudson River Railroad gained a majority of stock of the Lake Shore and Michigan Southern Railway. The line provided an ideal extension of the New York Central main line from Buffalo west to Chicago, along with the route across southern Ontario (Canada Southern Railway and Michigan Central Railroad). On December 22, 1914, the New York Central and Hudson River Railroad merged with the Lake Shore and Michigan Southern Railway to form a new New York Central Railroad.