A three-dimensional (3D) Pd-reduced graphene oxide framework (Pd-rGOF) with hierarchical macro- and mesoporous structures has been developed via covalence- and coordination-assisted self-assembly approach. In this facile fabrication process, GO was first cross-linked with triethylene tetramine (TETA) to form 3D GOF, in which well-dispersed and ultrasmall Pd nanoparticles (NPs) in situ grew and embedded the framework. The obtained nanopores, 3D Pd-rGOF, can act as nanoreactors to help the reaction substrates thoroughly contact with the surface of Pd NPs, thereby exhibiting high activity and selectivity toward the Tsuji–Trost reaction in water, with 99% conversion and selectivity for most substrates. Moreover, the 3D Pd-rGOF catalyst can be reused more than ten times without significant loss of activity, rendering this catalyst long-term stability. The abovementioned observations make the rGOF a universal platform to coordinate other noble metal ions (NM) to construct desired NM-rGOF nanocatalysts with improved activity, selectivity, and durability that can be used in a broad range of practical applications.