Katmai National Park is drained by several large rivers and creeks. These include the American Creek, Savonoski River, Ukak River, Rainbow River, Margot Creek, Headwaters Creek and Brooks River, which drain through the Naknek Lake and river system into Bristol Bay; King Salmon and Big Creeks, which drain into Naknek River; Katmai and Big Rivers, which drain into Shelikof Strait; Douglas and Kamishak rivers, which drain into Kamishak Bay; the Alagnak and Nonvianuk, which drain to the north into the Kvichak River and then into Bristol Bay; and the Egegik and King Salmon rivers, which drain from the southwest into Bristol Bay.

Major lakes associated with the park include Naknek, Grosvenor, Coville, Brooks, Idavain, Kulik, Nonvianuk, Hammersly, Murray, Dakavak, Katmai, Kaguyak, as well as a small part of the drainage feeding Becharof Lake, which is not itself within the park. There are also several unnamed lakes.

Water quality in all of these lakes and rivers remains essentially unaltered by man. Some bodies of water are heavily silted with glacial outwash sediments or volcanic ash. Others contain clear, unsilted water. Water levels in the larger lakes may vary seasonally by as many as seven feet.

American Creek, Big River, Brooks River, Funnel Creek, Hallo Creek, Headwaters Creek, Ikagluik Creek, Katmai River, Knife Creek (including Juhle Creek), and Kulik River have all been designated as potential rivers to be added to the National Wild and Scenic River System. This potential designation requires the National Park Service to manage/protect them as if they were Wild and Scenic until Congress brings them into the system or takes them off the potential designation list.