[2][3] The line followed the coastline, in contrast to the Boston & Maine's inland route through Massachusetts, and it served North Shore cities such as Lynn, Salem, Beverly, and Newburyport.

Construction on the railroad began in August 1837 after state loans and a change of route were approved in April.

[3] The first stretch to be built was from East Boston to Salem (13 mi or 21 km), completed August 27, 1838.

On April 28, 1847, the Eastern and the Boston & Maine co-leased the Portland, Saco & Portsmouth for a period of 99 years.

In 1850, the South Reading Branch Railroad opened, connecting the Eastern at Salem to the Boston & Maine at Wakefield, and in 1853, the Saugus Branch Railroad opened, connecting the Eastern at Lynn to the Boston & Maine at Malden.

It also disconnected the Saugus Branch from the Boston & Maine at Medford, redirecting it south to the Grand Junction in Everett.

In 1866, the Boston & Worcester bought the Grand Junction, but allowed the Eastern to keep its track rights for the sections it used as part of its main line.

On September 28, 1841, noted abolitionist Frederick Douglass and James N. Buffum (later mayor of Lynn) were forcibly ejected from a train at Lynn station after Douglass refused to sit in the segregated "Jim Crow car" in an early protest against the racial discrimination by the railroad.

[4] The actions by Douglass sparked further protests in Massachusetts against the discriminatory policies of the Eastern and other railroads.

In the 1970s, the Massachusetts Bay Transportation Authority (MBTA) acquired the Eastern Railroad's tracks along with several other Boston & Maine passenger lines.

In August 2019, New Hampshire purchased 9.6 miles (15.4 km) from Hampton to Portsmouth for $5 million for use as a rail trail.