The grand McLure Hotel opened on the corner of Market and Monroe (now 12th) streets in downtown Wheeling on March 4, 1852, shortly before the Baltimore & Ohio Railroad reached the city. John McLure had relocated from Pennsylvania in 1806 and became a prominent merchant and boat builder. He named his hostelry the McLure House, and it stayed in the family through four generations. The original hotel had 165 rooms and an open court with a watering trough and hitching posts. The McLure was one of the largest and best hotels in the region, and during the Civil War hosted Generals Frémont, Rosecrans, Sherman, and Grant. The founders of West Virginia often gathered there after debating issues of the day at the nearby U.S. Custom House, now known as West Virginia Independence Hall.

The hotel was remodeled in 1899 and grew to 225 rooms. Many famous persons have visited the McLure, among them Jenny Lind, Sara Bernhardt, and Jay Rockefeller. E. M. Statler, the founder of the Statler hotel chain and most famous hotelier of his day, started in the hotel business as a bellboy at the McLure and later became its manager. At least 11 presidents have been guests, including Eisenhower, Kennedy, and Nixon. On February 9, 1950, at the McLure, Sen. Joseph McCarthy delivered the famous speech that began the McCarthy era.

The original building was demolished, and an extensive renovation of the hotel was completed in 1985. In 1998, the McLure was purchased by Pelican International Properties and in November 1999 its name was changed to the Ramada Plaza City Center Hotel.