In January of 1862, Union colonel James A. Garfield led his brigade to Pikeville and used Ratliff's tavern, once located at present-day city park, as his base of operations. Garfield received his promotion to brigadier general while stationed at the tavern. His troops camped on this site until a flood forced them to the hill where the University of Pikeville is presently located. Ratliff's tavern was demolished in the 1930s but the site is commemorated by local historical markers detailing the area's Civil War history.

The Pikeville Methodist Episcopal Church, South was organized on Main Street in 1845, soon after the Methodist Episcopal Church's General Conference of 1844. In 1885, the church and representatives of Masonic Lodge No. 375 acquired a brick building at 339/341 Main Street; they occupied this structure until 1911 when the building was sold and used to purchase the current location. The current First Methodist Episcopal Church, South structure, located at 107 Main Street, was dedicated on June 22, 1913. In 1939, the Methodist Episcopal Church, South joined with two other denominations to form The Methodist Church. In 1968, it united with another denomination to form The United Methodist Church.

The Pikeville Post Office building was erected in 1931 using designs from supervising architect James A. Wetmore. In 1940, the federal courthouse building was added, reflecting colonial revival/Georgian-style government architecture. Both structures are contributing properties within Pikeville's historic district listed on the National Register. The Main Street post office branch continues to serve the community, having undergone local repairs and reopening updates in late 2020 following water damage.

The Hotel James Hatcher, built in 1931 on Main Street, contained 106 rooms. In its spacious lobby was a small museum displaying ox-yokes, handmade furniture, weapons, a huge fireplace, and utensils used by early settlers. The walls were covered with historical data, favorite mottos, and philosophical sayings. In one room, Hatcher kept on display his own coffin, which had been fashioned out of a walnut tree that once stood on the hotel's lawn. On July 3, 1934, First Lady Eleanor Roosevelt visited the hotel. It was demolished prior to 2005.

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This image shows the Pike County Jail as it appeared during the Hatfield trials in 1888-90. At least one jail was built after this one; it was demolished during the 1980s to make way for the current detention center. All of these jails were located behind the courthouse.

The old steamboat landing for Pikeville was located approximately where Division Street extends to Riverfill Parking Lot in modern times.