Two-photon processing presents a facile means to tailor the properties of materials in three-dimensions. A two-photon responsive metal–organic framework (MOF) has been realized through the incorporation of a photoactive linker into a MOF via a multivariate strategy. The resulting MOF exhibits a significant one-photon and two-photon excited fluorescence change in response to UV light and infrared femtosecond laser, enabling spatial modulation of the fluorescence property of the MOF. It thus demonstrates the capacity of two-photon patterning and imaging inside the crystal, and the formation of three-dimensional two-photon excited fluorescent structure in a high resolution.