Officials said an employee of a near-by Wendy's Restaurant reported the fire.
Officials said there are 96 rooms in the motel, but only 26 of them were occupied. They said 48 room suffered varied degrees of smoke and water damage.
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Flames were shooting from the roof and out of the windows on the second floor when the first fire truck arrived at the scene.
Two people were checked by Troy Fire Department paramedics for smoke inhalation, but were not taken to the hospital.
Guests at the motel said they all left in a calm mannter after the hotel's fire alarm sounded. The Troy Fire Department received mutual aid from Tipp City, Casstown, Piqua and Covington.
The Northern Miami Valley Chapter of the American Red Cross is helping 24 motel guests with lodging, clothing and travel.
At this time, there is no estimate on the amount of damage or a cause of the fire.
Assistant Troy Fire Chief Matt Simmons referred to the motel as a high-dollar loss.