MD 25 was one of the original state-numbered highway designation assigned by the Maryland State Roads Commission in 1927. By 1930, the Baltimore–Shawan portion of the highway had been widened to a minimum width of . Shortly after 1930, work began on a bridge over the Northern Central Railroad, whose right-of-way is now followed by the Baltimore Light RailLink, at Bare Hills; this structure was completed by 1934. MD 25's southern terminus was Charles Street by 1934 and MD 2 by 1956. The state highway's only major relocation was in 1962 and 1963 when the northern stub of the Jones Falls Expressway, now MD 25A, and the associated four-lane divided section of MD 25 in Brooklandville were constructed. With the completion of the Jones Falls Expressway, I-83 became the main highway from the north into downtown Baltimore and MD 25 was relegated to a local thoroughfare. MD 25 was closed for several months for the replacement of the highway's bridges over the Baltimore Light RailLink and Jones Falls at Bare Hills in 1991 and over I-695 near Brooklandville in 1996.