Construction, which lasted from 1928 to 1933, included the creation of viaducts, mail and express buildings, and utility structures: a power plant, water treatment facility, and roundhouse.

[25] Wank's original plan was traditional and featured Gothic architecture: large arches, vaulted ceilings, and conventional benches in long rows.

In 1931–32, Cret altered the design aesthetic:[25] thereafter, the terminal and its supporting buildings used modern architecture (later known as Art Deco), even in places not visible or open to the public.

[24][37] The building's architecture and design received mostly positive acclaim, though even in 1933 it was seen as possibly the last grand intercity train station built.

[41] The main facade, 500 feet (150 m) wide in total,[42] is the only portion visible from the plaza approach, and it is the building's most striking exterior feature.

[25] The entire east facade and the outer walls of the entrance drives are faced with a light, fine-grained Indiana limestone, with a low granite base.

The flues act as sound channels, allowing people 30 meters apart at the base of each arch, by symmetrical drinking fountains, to hold a private conversation with ease.

The room carried on the same marble pattern of the rotunda walls, and had a segmental arch ceiling 36 feet, 8.5 inches above the floor at the crown, painted in shades of yellow from pale lemon to orange.

Instead it had American Oak Leather-upholstered settees and chairs in aluminum frames, placed in twelve concentric groups of 46 seats, each around a small, round teakwood table.

[54] In late 2019, the museum center opened the space for a few weeks for the holiday season, staffed by Cincinnati Railroad Club volunteers.

[56][22] The room was designed by William E. Hentschel of the Rookwood Pottery Company, and utilized mint green, pale gray, and mauve tiles.

The lunchroom, now known as the Losantiville Dining Room, has relatively high yellow Verona marble walls, with a band of green above it, and a chocolate-brown ceiling.

The ceiling mural in the room's vestibule was also cleaned, and new green terrazzo was installed in the floor to show where the serpentine lunch counters were.

[6] The men's and women's waiting rooms both used distinctive marbles, and featured wainscoting, with the walls above made of plywood or flexwood showing the natural grain, or in designs.

The men's room walls feature a railroad motif, using zebrawood, walnut, and holly; the women's lounge had panels of zebra and madrone wood.

The space also included or led to restrooms, telephone booths, a shoeshine room, barber shop, newsstand, train bulletins, and a soda fountain.

Reiss explained that the south mural symbolizes the country's development from Native American inhabitance to the late industrial era, with a history of transportation in the background.

The pioneer family depicted symbolizes "the courage and fortitude of the man; the loyalty and love of the mother; the wondering romance of the past and future America in the eyes of the boy".

The African American laborers were drawn from Union Terminal construction workers, while the Blackfeet natives were copied from sketches Reiss made earlier while visiting the group.

It included five decorative clocks made of tile, together representing five of the United States's time zones: Pacific, Mountain, Central, Eastern, and Atlantic.

The mural also included two Nicolosi globular projections of the world, with the Americas on the left side and Europe, Africa, Asia and Australia on the right.

[68] Two Reiss murals are located in the checking lobby, by the current entrance to the Omnimax theater and historically an intermediate space between the rotunda and train concourse.

The south mural, left to right, features Russell Wilson (Cincinnati mayor at the project's completion in 1933), H. A. Worcester (first Union Terminal Co. president), and Clarence A. Dykstra (city manager in 1933).

After the concourse's demolition, they were moved to each side of the entrance of the Cincinnati History Library, on the mezzanine level (the space is now occupied by the Holocaust & Humanity Center).

[33] The terminal was put into emergency operation on March 19, 1933, because another Ohio River flood forced the closure of four train stations in the city.

At this event, B&O director John J. Cornwell notably stated that passenger stations were declining in use, and that the building's completion came after its need had passed.

[45] The scheduled closure left the terminal's fate uncertain, leading multiple efforts to bring the topic to public attention in mid-to-late October 1972.

[31] The last passenger train departed on October 28, 1972,[22] and Amtrak abandoned the terminal and opened a smaller station nearby on the following day.

The entrance to the train concourse was renovated into the Omnimax theater, and the men's lounge became Amtrak's waiting room and ticket counter.

[88] In January 2019, the terminal gained another museum as a tenant, the Nancy & David Wolf Holocaust and Humanity Center, in the former space of the History Library.