After grappling with financial difficulties for many years, the company opened service between Bridge Street in Grand Rapids to Cedar Springs, Michigan, on December 25, 1867, a distance of about 20 miles (32 km).

By 1869 the railroad was again in trouble with its creditors, and the courts appointed a receiver, Jesse L. Williams of Fort Wayne, Indiana, to control the company.

Under Williams' direction the Continental Improvement Company was hired on May 1, 1869, to complete the line between Fort Wayne and Little Traverse Bay in Michigan.

Fifty-one days later, on June 21, 1869, the Continental Improvement Company had laid the last rail connecting Cedar Springs to Morley, Michigan.

In 1886 the company added an "airline" branch from Grand Rapids to Muskegon, Michigan, allowing travel between the two cities in about 1 hour.

In 1891 the Grand Rapids and Indiana Railroad featured the longest North-South line in the country.

During the 1990s much of the old railroad right of way between the north side of Grand Rapids and Cadillac, Michigan, was turned into the White Pine Trail State Park.

A portion of the old railroad right of way just north of Vicksburg is part of the Vicksburg Trailway from Towline Ave to East TU Ave.[2] The portion of the right of way south of Kalamazoo is still in service as a Watco Grand Elk Railroad spur serving Pfizer portage plant.