The Mersey River flows through Kejimkujik National Park in Nova Scotia, running from the park's interior southward to the town of Liverpool, where it empties into the Atlantic. The river offers a wide range of paddling experiences, from calm stillwater sections to moving water runs and rapids, making it suitable for paddlers of varying skill levels depending on which section is chosen.

The stretch within Kejimkujik National Park is characterized by quiet, dark-brown bog-fed waters, lushly vegetated islands, overhanging red maples, and abundant wildlife. Paddlers commonly encounter turtles, beavers, muskrat, great blue herons, bullfrogs, and white-tailed deer. The primary access point within the park is Jake's Landing, where canoe and kayak rentals are available through Whynot Adventure. A second launch point exists at the Visitor Centre, from which a short upstream trip is possible. The park section is well-suited to beginners and families, with children as young as five participating in guided tours.

The full Mersey River route, as documented by the Municipality of Annapolis County, is not recommended for novice or intermediate paddlers. It combines quiet stillwaters, moving water runs, and large lakes, with portages required at various points. The section between Kempton Lake and Kejimkujik Lake can become difficult during low water, presenting long stretches of exposed rock. Helmets are recommended for running rapids, and longer rope is advisable for lining through rougher sections. Access points along the upper river include Four Mile Runs and Three Mile Runs, both reached via gravel roads off Highway 8.

The whitewater section within the park includes features such as Mill Falls and The Ledges, where the river flows over a series of ledges that can be scouted from a footbridge. Portaging at The Ledges is easiest on river left. Additional access points within the park include the bridge on Jeremy's Bay Campground Road and the Mersey River Trailhead.

Paddlers camping overnight within Kejimkujik National Park must reserve numbered backcountry campsites in advance. Blue-green algae may be present in the park's lakes and waterways, and paddlers should avoid areas with visible concentrations. The lower river near Liverpool offers calm, sheltered paddling through the town's inner harbour and toward the Atlantic coastline.

The Mersey River has served as a travel corridor for the Mi'kmaq people for centuries, connecting the interior to the coast, and this cultural history is a notable aspect of the paddling experience throughout the river's length.