The Red Line is Boston's third-oldest subway. It was originally known as the Cambridge-Dorchester Subway. The section from Harvard to Park Street via the Cambridge Tunnel, Longfellow Bridge, and Beacon Hill Tunnel opened in 1912. The Dorchester Tunnel from Park Street to Andrew opened as far as Broadway in 1917 and the rest of the way to Andrew in 1918. In 1928 the Dorchester Extension opened to Ashmont, using the right-of-way of the New York, New Haven & Hartford RR's Shawmut Branch (the portion of the branch from Ashmont to Mattapan became the High Speed Trolley line). In 1985 an extension from Harvard to the current northern terminus of Alewife opened. At the same time, the Eliot Square Shops were abandoned and replaced by the new Cabot Shops near South Station. The South Shore Extension from JFK/UMass to Quincy Center was opened in 1971, and finished to Braintree in 1980.

There are currently four types of cars on the Red Line. The oldest are the #1 South Shore cars in the 01500- and 01600-series, which were built by Pullman-Standard in 1969. Next are the #2 cars in the 01700 series, built by UTDC in 1987-9. These are virtually identical to the #1 cars (UTDC acquired the design from Pullman-Standard), the major differences being flat roofs (instead of corrugated roofs) and a larger "railfan" window at the front of the car. Newest are the #3 cars in the 01800 series, built by Bombardier in 1993-4. The 01500s were built as double-ended cars, but lost the second cab when they were rebuilt in the 1980s. All the other cars were built as single-end cars. The 01600s and 01800s were built as married pairs; the 01500s and 01700s can operate as single units, but in practice also run as married pairs. Red Line cars are the largest in Boston, as the tunnels were built with very wide clearances (for their time).