Plans for a railway line between Rome and the Adriatic coast began in 1846 in the Papal state, after the death of Pope Gregory XVI, who strongly opposed rail.

The construction of the new railway was authorized on 7 November 1846 by the new Pope Pius IX, to link Rome with the main port on the Adriatic sea, Ancona.

The project was initially named Strada Ferrata «Pio Centrale» in honor of the Pope, but was finished only on 29 April 1866, under the newly born Kingdom of Italy.

However, the partially completed line was opened since 1865, with trains operated by Società per le strade ferrate romane (SSFR).

The line was subsequently incorporated into the Adriatic network and managed by Società Italiana per le strade ferrate meridionali (Italian company for southern railways), which doubled tracks between Rome and Orte in 1890.