The first grist and sawmills were built in 1800 in Middlesex by Henry Perkins at the "Narrowa" where Middlesex Village now stands. Soon after were built an oil mill and a clothing-works mill. The livelyhood of the settlers in this area was largely based on agriculture and forestry. By 1879 there were three stores in Middlesex and no physician. There were also three meeting houses, one located in Shady Rill.
Running parallel to Winooski River along the southern border of Middlesex is Interstate 89. Also following this route is the Vermont Railway. Smaller roads include, Colby, McColough, Great Brook, Upper and Lower Barnet Hill, Upper and Lower Sunny Brook, Davy, Portal, East Hill, Bolduc Dolan, Culver Hill, Molly Supple Hill, French, Shady Rill, Macey, Woods, Bear Old Farm, East and North Bear Swamp, Center, Notch, Middlesex Notch, Chase, Woods, and others. Route 2 cuts through the eastern corner of Middlesex by way of Putnamville.