The route runs southwest from downtown Boston along Tremont Street, ending at the Ruggles bus terminal and Orange Line transfer point.

Soon afterward, in 1859, a branch of this line was built west along Tremont Street to Brookline (this later became part of the 66).

A shuttle service was kept between the portal and Boylston, with one double-ended PCC streetcar on each track.

[4] This terminus was kept until June 1972, when service was extended north around Boston Common to Park Street.

With the opening of the new southern portion of the Orange Line in May 1987, the south end of the 43 was truncated to Ruggles, with extensions of the 22 and 29 providing service between Ruggles and Egleston (the latter having been reduced to a bus stop with the closure of the Washington Street Elevated).