For the first time, a ∼100 % sulfonic acid functionalized metal–organic framework (MOF), MIL‐101‐SO3H, with giant pores has been prepared by a hydrothermal process followed by a facile postsynthetic HCl treatment strategy. The replete readily accessible Lewis acidic and especially Brønsted acidic sites distributed throughout the framework as well as high stability endow the resultant MOF exceptionally high efficiency and recyclability, which surpass all other MOF‐based catalysts, for the ring opening of epoxides with alcohols (especially, methanol) as nucleophiles under ambient conditions. Metal–organic frameworks: A fully sulfonic acid functionalized metal–organic framework (MOF), MIL‐101‐SO3H, with giant pores has been prepared by a postsynthetic HCl treatment strategy. The resultant MOF replete with readily accessible Brønsted acid sites exhibits exceptionally high efficiency and recyclability for the alcoholysis of epoxides under ambient conditions (see scheme).