Its headwaters are on the slopes of Cougar, Squak, Tiger, and Taylor mountains in the Issaquah Alps.

[3] Issaquah Creek's drainage basin is over 75% forest land and less than 10% urbanized or cleared.

The upper and middle portions of the basin have been identified as a Regionally Significant Resource area due to their exceptional fish habitat and undeveloped character.

Issaquah Creek and its tributaries support Chinook, coho salmon (and resident kokanee), coastal cutthroat trout.

Chinook and coho are reared by the state Issaquah Salmon Hatchery, located three miles upstream from the creek's mouth.