Prior to being discontinued in 2019, the Hoosier State provided service on the portion of the Cardinal's route between Indianapolis and Chicago on the other four days of the week.

The George Washington, the C&O's flagship train, was a long-distance sleeper that ran between Cincinnati and—via a split in Charlottesville, Virginia—Washington, D.C. and Newport News, Virginia.

[14]: 38  The eastern terminus was briefly extended to Boston, giving the Northeast Corridor a one-seat ride to Chicago.

During the early Amtrak era, the Riley was plagued by the poor condition of ex-New York Central track in Indiana.

[14]: 256  By 1974, Amtrak rerouted it off Penn Central track altogether; by then, the trackage had deteriorated so badly that the Riley was limited to 10 mph (16 km/h) for much of its route through Indiana.

[15] A number of long-distance trains running along former Penn Central trackage in the Midwest were plagued by similar problems.

From March 29, 2018, to November 8, 2018, due to continuing construction at New York Penn Station, the Cardinal's eastern terminus was temporarily moved to Washington.

Amtrak ultimately discontinued the Kentucky Cardinal on July 4, 2003, and brought back the Hoosier State on the pre-1999 schedule.

Railfan and Railroad magazine also suggested that the train be rerouted to St. Louis, with a separate section bound for Chicago.

[22] The January 2011 issue of Trains later revealed that Amtrak would scrap re-routing and Superliner conversion and instead adopt not only daily service, but also purchasing dome cars to be used along the Chicago-Washington, D.C., portion of the trip.

This problem also applied to the planned-but-failed Greenbrier Presidential Express train, which would also have traversed the Buckingham Branch on a weekly basis.

[27] The Chicago Region Environmental and Transportation Efficiency Program (CREATE) has received funding under a public–private partnership (P3) for the 75th Street Corridor with construction beginning in October 2018 and is scheduled to be finished by 2025.

[29] In June 2021, Senator Jon Tester of Montana added an amendment to the Surface Transportation Investment Act of 2021 which would require the Department of Transportation (not Amtrak itself) to evaluate daily service on all less frequent long-distance trains, meaning the Cardinal and Sunset Limited.

[34] In mid-2023, Amtrak applied for a federal grant to operate the Cardinal daily and increase speeds between Indianapolis and Dyer.

[35] In December 2023 the daily Cardinal project was granted $500,000 from the IIJA through the Federal Railroad Administration's Corridor Identification and Development Program.

[37] As a result, its route was truncated to end in Washington D.C., as Superliners cannot operate on the Northeast Corridor due to low tunnel clearances in Baltimore and New York City.

Subsequent fleet shortages shortened the Cardinal further, and at one point, the train was running with two or three Amfleet II coaches and a combined diner-lounge car.

After an early morning departure from New York and traveling south down the Northeast Corridor, the train passes through Virginia's rolling horse country, across the Blue Ridge and the Shenandoah Valley.

Westbound, the train travels at night from Charleston, West Virginia, on to Indianapolis, where it arrives at about dawn, reaching Chicago mid-morning.