The Toledo and Ann Arbor Railroad, founded by James Mitchell Ashley, completed the line in 1878.

The Toledo, Ann Arbor and Grand Trunk Railroad built 15 miles (24 km) north to South Lyon via Leland.

Using another new company, the Toledo, Ann Arbor and Lake Michigan Railway, the line was extended west from Cadillac to Copemish.

[14] The Toledo, Ann Arbor and North Michigan Railroad entered bankruptcy during the Panic of 1893, and James Ashley resigned as president in 1894.

[16] A more significant change came in 1897, when the line was re-routed in Gratiot County to serve Alma directly, bypassing St. Louis.

[19] Also in 1897 the Ann Arbor built a new station in Toledo at Cherry and Seneca, 2.5 miles (4.0 km) from the main line.

The bankrupt estate retained ownership of the line north of Cadillac to Frankfort and between Durand and Ann Arbor.

Finally, the state of Michigan bought the line between Ann Arbor and Toledo, and also between Cadillac and Ashley.

[26][27] The Grand Trunk Western promptly abandoned most the ex-Ann Arbor's parallel line between Durand and Owosso.

[31][c] Train ferry service out of Frankfort ended in April 1982 amid a financial dispute between the Michigan Interstate Railway and the state.

Beginning that October, the Michigan Interstate stopped operating north of Ann Arbor, and the state brought in two new operators: the Michigan Northern Railway for the line north of Alma, and the Tuscola and Saginaw Bay Railway for the line between Alma and Ann Arbor.

[35] At the same time, the state acquired the Grand Trunk Western's remaining 22 miles (35 km) between Ashley and Owosso.

[39] Nothing came of a proposal by a new company, the Elberta, Betsie River Valley and Michigan Railway, to resume service in the early 1990s.

[40] A proposal to convert the line between Frankfort and Thompsonville into a rail trail was stalled for years by litigation over property ownership around Crystal Lake.