SR 25 begins west of Porter, where NH 25 crosses the Maine-New Hampshire border.

The western part of the highway runs along the Ossipee River on the southern edge of town.

The highway crosses into Portland and immediately interchanges with the Maine Turnpike (I-95) at exit 47, thereafter meeting its business route and proceeding into downtown on Brighton Avenue.

An unnumbered extension of Larrabee Road continues to the north with access to the Maine Turnpike at exit 48.

In 2002, the Westbrook Arterial was extended to Rand Road in Portland, passing over the Turnpike with a new direct interchange, exit 47.

The routes continue this way until reaching the Westbrook Arterial, which SR 25 turns onto to bypass the city to the south, towards the Maine Turnpike.

Until the Westbrook Arterial was extended to Rand Road in 2007 (and SR 25 moved onto the new alignment), this intersection was the eastern terminus of the business route.