The Manu region experiences distinctive wet and dry seasons.

The rainy season lasts from December through March and is the period in which most of the area's 2m (6ft) of annual rainfall occurs. The "dry" season, from April to November, is often marked by rainless periods which can last for several weeks, although downpours should be expected at any time of year. Although short-lived, these showers are often quite heavy and can cause the rivers to swell unexpectedly. August, September, and October are usually the driest months.

Daytime temperatures in the dry season range from 32ºC (90ºF) with the nights averaging 25ºC (77ºF). Unexpected cold fronts known as "friajes" can blow in from the Andes at any time of year, especially in the dry season. This phenomenon brings between one and three days of rain, with daytime highs falling to 16ºC (60ºF) and nighttime temperatures to around 10ºC (50ºF). Wildlife is typically not active during a "friaje", but becomes quite active again immediately afterwards.