In 1862, after the society had gone through several temporary facilities, a building was constructed in the Back Bay area of the city and dubbed the New England Museum of Natural History.

The museum was located next to the original Rogers Building of the Massachusetts Institute of Technology (MIT), and both neoclassical structures were designed by William G. Preston.

Under the leadership of Bradford Washburn, the society negotiated with the Metropolitan District Commission for a 99-year lease of the land on the Charles River Dam Bridge, now known as Science Park.

The Science Park/West End MBTA infill station was opened in August 1955, allowing easier access to the museum by public transportation.

In 2013, the Museum of Science was the venue for the first joint session of the Boston and Cambridge city councils, to discuss policy measures to improve retention of talented recent university graduates in the area.

[8] The audio kinetic sculpture Archimedean Excogitation was moved to the atrium to make way for a new exhibit in the lower lobby called the Yawkey Gallery on the Charles River.

This is a new, flexible meeting space enclosed in glass, and replaces an earlier windowless physical volume which had turned a blank wall to the Charles River.

[12][13] In front of the museum, a memorial to Leonard Nimoy, the television and movie actor who grew up nearby in the West End of Boston, is planned for installation.

Live animals shown have included tarantulas, hissing cockroaches, and axolotls, as well as better-known birds and furry mammals, many of which the museum gained after they were surrendered, confiscated, rescued, or rehabilitated.

The design center includes about a dozen activities for visitors to attempt while learning about the engineering process run twice a day from 10am-12pm and from 2pm–4pm during the school year, and also 4:30pm–6:30pm during the summer.

Cahners ComputerPlace, previously located in the Blue Wing, Level 1, housed displays ranging from educational video games to an interactive AIBO ERS-7 robot.