The town has two main hamlets, Wynantskill in the northeastern corner and Defreestville in the southern portion of the town. Both have strong identities and hinder efforts by the town to have a centralized identity. Also hindering a unified town image is that North Greenbush consists of parts of four different school districts, only one of which (a one room schoolhouse) carries the town's name; two fire departments (Wynantskill and Defreestville); and three ZIP codes (Troy, Rensselaer, and Wynantskill). North Greenbush is home to the southern part of the Hudson Valley Community College (HVCC) campus, including the Joseph L. Bruno Stadium, home to the Tri-City Valley Cats minor league baseball team; the RPI Tech Park; the La Salle Institute; the New York State National Guard Armory, headquarters for the Rainbow Division; and various Rensselaer County government institutions.
North Greenbush was part of the Manor of Rensselaerswyck, and Albany County prior to Rensselaer County's creation in 1791. North Greenbush was created on February 23, 1855 from the town of Greenbush at the same time as the town of Clinton (today East Greenbush). At this time North Greenbush occupied more than what it does today, it also covered what is now the northern section of the city of Rensselaer and the southern section of the city of Troy.
The earliest settlers, in the early 1620s settled in Bath, a part of the town annexed to Rensselaer in 1902. Some settlement in what is today North Greenbush may have occurred in the 17th century as well, but most significant early settlement occurred just prior to the US Revolutionary War. Early settlements in the town were at Bath, Wynantskill, and Defreestville. In 1874 Bath became incorporated as a village, and in 1902 it was annexed to Rensselaer. Wynantskill, in the northeastern corner of the town was first settled around the end of the 18th century with a Dutch Reformed Church established around 1794, and a post office was established in 1820. Defreestville was originally called Blooming Grove until around 1830 when it was changed due to confusion with another Blooming Grove in Orange County, New York, it was named Defreestville for David M. De Freest and family who owned a tavern there. Defreestville and Wynantskill continue to be important hamlets in the town. Snyders Lake would in the 20th century also become an important community. Snyders Lake was developed as summer residences and continues to lack a central business district.
During the 20th century North Greenbush would begin to see more development thanks to an improved transportation infrastructure which led to increased suburban residential, office, and retail growth based on the automobile. In 1931 the road between Troy and East Greenbush was widened and the right-of-way straightened as US Route 4. The older, narrower, winding residential parts of the road were bypassed and is today's Bloomingrove Drive. Starting in the 1940s and 50s suburban growth along Route 4 would begin to displace farms and local businesses with national chains with an automobile oriented pattern of growth. This suburban growth would be encouraged by the construction of Interstate 90 (I-90) and the Patroon Island Bridge in the 1960s making North Greenbush an easy commute to Albany. I-90 would not have a direct exit to North Greenbush until 1996 though, when Exit 8 was constructed connecting US 4 and NY Route 43 to the interstate. In the 1970s Rensselaer Polytechnic Institute (RPI) began developing the RPI Tech Park on Route 4 as a business incubator, today it has over of office space. A connector highway will eventually also go from Exit 8 parallel to US 4 north through the RPI Tech Park and meet US 4 near Hudson Valley Community College (HVCC) at the Troy city line.
Not all suburban growth has been well received in the town however. In the late 1990s the RPI Tech Park became the focus of regional and state-wide push to get a chip fabrication factory (chip fab plant) built. The RPI Tech Park site originally met little opposition from the town. But as time progressed opposition grew in response to concerns about potential impacts on traffic and the environment. The RPI Tech Park site, which by October 1999 had become one of only nine sites still being marketed by the state, was terminated when the North Greenbush town council voted to terminate the review process. Another instance of NIMBY opposition to development occurred after the construction of I-90's Exit 8 when that location became well-primed for commercial development. Local developer Frank Nigro with Nigro Company proposed a high-end shopping center for the north-east corner of the intersection of routes 4 and 43. This led to lawsuits and a failed push by residents of Defreestville to incorporate as a village in order to stop the development; and a counter-move by the developer and certain landowners to attempt annexation to the neighboring city of Rensselaer where the development would be better received.