The Junction Railroad was chartered March 2, 1846, to build from Cleveland west to Toledo. The Toledo, Norwalk and Cleveland Railroad was chartered March 7, 1850, to build from Toledo east to Grafton on the Cleveland, Columbus and Cincinnati Railroad. The latter company opened on January 24, 1853, finally forming a continuous Buffalo-Chicago line.
On September 1 the two companies merged to form the Cleveland and Toledo Railroad, with the Junction Railroad becoming the Northern Division and the Toledo, Norwalk and Cleveland the Southern Division. The Northern Division opened from Cleveland west to Sandusky on October 24, 1853, and the rest of the way to Toledo on April 24, 1855. The Northern Division was abandoned west of Sandusky due to lack of business, but the track was relaid in 1872, merging with the Southern Division at Millbury, east of Toledo. In 1866 the Southern Division east of Oberlin was abandoned and a new line was built to Elyria on the Northern Division, ending the use of the Cleveland, Columbus and Cincinnati Railroad.
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.