The route proceeds north along Sykes Street, crossing through downtown Palmer.

Leaving downtown Palmer, the route crosses over some railroad tracks and the two-lane road makes a dart to the northwest before Bourne Street.

At Pine Street, Route 181 crosses north through Bondsville, at the north end of Bondsville, the route leaves Hampden County for Hampshire County.

[2] Route 181 passes a local community of residences, serving as the main north–south street.

After a northwestern stretch through the town of Belchertown, Route 181 enters downtown Belchertown, retaining the Mill Valley Road name until its junction with South Main Street, where it takes the latter as a moniker, proceeding northwest another block to US 202 and Route 21 (Maple Street).