I-95 continues north along its concurrency with the Maine Turnpike (which was I-495 prior to 2004) through Gray to Auburn and Lewiston, bypassing the latter two cities to the south.

The highway runs along the northern edge of Bangor's center, then turns northeast, following the Penobscot River past Orono and Old Town.

Near Lincoln, I-95 runs north through uninhabited forest land, crossing the Penobscot River at Medway.

The highway goes northeast and east, passing a series of small Aroostook County farming towns before reaching Houlton, where it connects to US 2 and New Brunswick Route 95 at the international border.

In 1953, the MTA began construction on an extension to the state capital at Augusta using the former right-of-way of the Portland–Lewiston Interurban railway from Portland through West Falmouth.

The remaining sections to be built—from Augusta to Fort Kent—would be publicly funded freeways instead of toll roads under the MTA.

Today, this highway, which ends at Houlton instead of Fort Kent, is signed as I-95 throughout and the Maine Turnpike between the New Hampshire line at Kittery and the junction with US 202 near Augusta.

In 2015, the MTA purchased the segment from the Piscataqua River Bridge to milemarker 2.2 of I-95 from the Maine Department of Transportation (MaineDOT).

In 1974, as part of a federal mandate, the speed limit was reduced to 55 mph (89 km/h), with a new law including a "less than 10 over" violation.

[12] The turnpike joined the E-ZPass electronic toll collection network in 2005, replacing the former Maine-only system designated Transpass that was implemented in 1997.

[14] There are eleven total rest areas on I-95 in Maine, five of which are full service plazas operated by the MTA.

The MTA is planning to reestablish the exit at this location by 2022 in order to relieve traffic congestion at the intersection of I-195 and Industrial Park Road, which can often back up to I-95.

There are 24-hour restrooms at all four locations, while the Hampden facilities each feature a state-operated Maine information center available during daytime hours.

A final rest area, which also contained a state-operated Maine information center, was located in Houlton, and was accessible from both directions of I-95 by taking exit 302.

In such an event, electronic signs will be activated and flaggers deployed to direct drivers to use the appropriate emergency route to lead them around the closure and maintain traffic flow.