The river's uppermost reach leaves the lake and flows through the city of Whitefish for 2.5 miles (4.0 km).

Small Cow Creek flows southwest 4.5 miles (7.2 km) and discharges into the river 2 miles (3.2 km) downstream from Whitefish Lake.

[6] The Montana Department of Environmental Quality (DEQ) determined in 2014 that the Whitefish River was temperature-impaired, meaning that high temperature impairs aquatic life and that a reduction in water temperature of 0.99 °F was recommended.

[7][additional citation(s) needed] Bull trout (Salvelinus confluentus) and westslope cutthroat trout (Oncorhynchus clarki lewisi) are considers indicator species of stream health, and are present in the Whitefish River, although in greatly diminished numbers.

[6] Other native fish species include the river's namesake mountain whitefish (Prosopium williamsoni), largescale sucker ((Catostomus macrocheilus)), longnose sucker ((Catostomus catostomus)), northern pikeminnow ((Ptychocheilus oregonensis)), peamouth chub (Mylocheilus caurinus,), redside shiner ((Richardsonius balteatus)), and slimy sculpin (Cottus cognatus).