The Manchester and Lawrence was chartered in 1847 and opened in November 1849. It leased the newly built Methuen Branch from the Boston and Maine Railroad which opened in August 1849 and ran from South Lawrence through Methuen to the state line where the two lines met.
The B&M tried to lease the M&L, but the company leased itself to the Concord Railroad in 1850. This still helped the B&M as the railroad opened up a second Manchester to Boston route that helped the B&M compete with the combined Nashua and Lowell and Boston and Lowell Railroads. Within 1887, the contract was terminated, and the B&M gained control of the line.
In the 20th century, the line was relegated to local freight. Passenger service on the line dropped to one round trip per day until 1953 when regular passenger service ended. Special summer trains ran to Rockingham Park in Salem for the horse races until 1960 when that service stopped.