Topography varies sharply among the six distinct regions of Alaska. In the southeast is a narrow coastal panhandle cut off from the main Alaskan landmass by the St. Elias Range. This region, featuring numerous mountain peaks of 10,000 ft (3,000 m) in elevation, is paralleled by the Alexander Archipelago. South-central Alaska, which covers a 700-mi (1,100-km) area along the Gulf of Alaska, includes the Kenai Peninsula and Cook Inlet, a great arm of the Pacific penetrating some 200 mi (320 km) to Anchorage. The southwestern region includes the Alaska Peninsula, filled with lightly wooded, rugged peaks; and the 1,700-mi (2,700-km) sweep of the Aleutian islands, barren masses of volcanic origin. Western Alaska extends from Bristol Bay to the Seward Peninsula, an immense tundra dotted with lakes and containing the deltas of the Yukon and Kuskokwim rivers, the longest in the state at 1,900 mi (3,058 km) and 680 mi (1,094 km), respectively. Interior Alaska extends north of the Alaska Range and south of the Brooks Range, including most of the drainage of the Yukon and its major tributaries, the Tanana and Porcupine rivers. The Arctic region extends from Kotzebue, north of the Seward Peninsula, east to Canada. From the northern slopes of the Brooks Range, the elevation falls to the Arctic Ocean.

The 11 highest mountains in the US—including the highest in North America, Mt. McKinley (20,320 ft/6,198 m), located in the Alaska Range—are in the state, which also contains half the world's glaciers; the largest, Malaspina, covers more area than the entire state of Rhode Island. Ice fields cover 4% of the state. Alaska has more than three million lakes larger than 20 acres (eight hectares), and more than one-fourth of all the inland water wholly within the US lies inside the state's borders. The largest lake is Iliamna, occupying about 1,000 sq mi (2,600 sq km).

The most powerful earthquake in US recorded history, measuring 8.5 on the Richter scale, struck the Anchorage region on 27 March 1964, resulting in 114 deaths and $500 million in property damage in Alaska and along the US west coast.