Diverse species of flora and fauna inhabit the area, which is subject to frequent snowfall, occasional rain, and extreme temperature variation between seasons.

After satellite imagery detected ground inflation near South Sister in 2001, the United States Geological Survey improved monitoring in the immediate area.

Air from the Pacific Ocean rises over the western slopes, which causes it to cool and dump its moisture as rain (or snow in the winter).

Finally, around the summit of South Sister, in a clockwise direction, are the Prouty, Lewis, Clark, Lost Creek, and Eugene Glaciers.

[21] When Little Ice Age glaciers retreated during the 20th century, water filled in the spaces left behind, forming moraine-dammed lakes, which are more common in the Three Sisters Wilderness than anywhere else in the contiguous U.S.[22] The local area has a history of flash floods, including an event on October 7, 1966, caused by a sudden avalanche; this flash flood reached the Cascade Lakes Scenic Byway.

[14][30] The Three Sisters form the leading edge of a rhyolitic crustal-melting anomaly, which might be explained by a combination of mantle flow (movement of Earth's solid silicate mantle layer caused by convection currents) and decompression that has generated similar melting and rhyolitic volcanism nearby for the past 16 million years.

[33] Among the most active volcanic areas in the Cascades and one of the most densely populated volcanic centers in the world,[34] the Three Sisters region includes nearby peaks such as Belknap Crater, Mount Washington, Black Butte, and Three Fingered Jack to the north, and Broken Top and Mount Bachelor to the south.

[33][35] Most of the surrounding volcanoes consist of mafic (basaltic) lavas;[35] only South and Middle Sister have an abundance of silicic rocks such as andesite, dacite, and rhyodacite.

Cinder cones accumulate from the airfall of many pyroclastic rock fragments of various sizes,[39] while the viscous rhyolite domes extrude onto the surface like toothpaste.

[43] North Sister's lava flows demonstrate similar compositions throughout the mountain's long eruptive history.

[45][46] North Sister possesses more dikes than any similar Cascade peak, caused by lava intruding into pre-existing rocks.

[42] One of the earliest major eruptive events (about 38,000 years ago) produced the rhyolite of Obsidian Cliffs on the mountain's northwestern flank.

[57] These eruptions generated pyroclastic flows and lava domes from vents on the northern, southern, eastern, and southeastern sides of the volcano.

[62] Despite its relatively young age, every part of South Sister other than its peak has undergone significant erosion due to Pleistocene and Holocene glaciation.

During the Holocene, smaller glaciers formed, alternating between advance and retreat, depositing moraines and till between 7,000 and 9,000 ft (2,100 and 2,700 m) on the mountain.

[64] The Lewis and Clark glaciers have cirques, or glacial valleys, that made the outer walls of the crater rim significantly steeper.

[66] In the 1940s, Howel Williams completed an analysis of the Three Sisters vicinity and concluded that Multnomah had never existed, instead demonstrating that each volcano in the area possessed its own individual eruptive history.

[66][67] Williams' 1944 paper defined the basic outline of the Three Sisters vicinity, though he lacked access to chemical techniques and radiometric dating.

[60] An eruption from South Sister would pose a threat to nearby life, as the proximal danger zone extends 1.2 to 6.2 mi (2 to 10 km) from the volcano's summits.

[69] During an eruption, tephra could accumulate to 1 to 2 in (25 to 51 millimetres) in the city of Bend, and mudflows and pyroclastic flows could run down the sides of the mountain, threatening any life in their paths.

[73] In 2001, scientists inferred magmatic activity near South Sister from InSAR satellite data that showed uplift of the ground surface in an area centered approximately 3 mi (4.8 km) west of the mountain.

[75] A 2011 study described the cumulative magma intrusion as 50 to 70 million cubic metres (1.8×10^9 to 2.5×10^9 cu ft) in volume.

[77] GPS and satellite observations showed that the rate of uplift west of South Sister gradually decreased from 2001 to 2020.

[78][79] Mountain hemlock trees dominate the forest in this area,[82] while meadows sustain sedges, dwarf willows, tufted hairgrass,[78][79] lupine, red paintbrush, and Newberry knotweed.

Bobcats, cougars, coyotes, wolverines, martens, badgers, weasels, bald eagles, and several hawk species are many of the predators throughout the Three Sisters area.

[84] The Three Sisters area was occupied by Amerindians since the end of the last glaciation, mainly the Northern Paiute to the east and Molala to the west.

[86] As the Willamette Valley was gradually colonized in the 1840s, Euro-Americans approached the summits from the west and probably named them individually at that time.

[95] The following year, at the instigation of Forest Service employee Bob Marshall, it was expanded by 55,620 acres (225 km2) in the French Pete Creek basin.

Due to extensive erosion and rockfall, North Sister is the most dangerous climb of the three peaks,[96] and is often informally called the "Beast of the Cascades".

[98] The first recorded ascent of North Sister was made in 1857 by six people, including Oregon politicians George Lemuel Woods and James McBride, according to a story published in Overland Monthly in 1870.