AMPA-type glutamate receptors (AMPARs) are responsible for a wide variety of processes in the mammalian brain including fast excitatory neurotransmission, postsynaptic plasticity or synapse development. Here we show by using comprehensive and quantitative proteomic analyses that native AMPARs are macromolecular complexes with an unappreciated large molecular diversity. This diversity results from co-assembly of the known AMPAR subunits, pore-forming GluA and three types of auxiliary proteins, with 21 newly identified constituents, mostly secreted proteins or transmembrane proteins of different classes. Their integration at distinct abundance and stability establishes the heteromultimeric architecture of native AMPAR complexes: a defined core with a variable periphery resulting in an apparent molecular mass between 0.6 and 1 MDa. Co-assembly of the newly identified constituents changes the gating properties of AMPARs and provides novel molecular links to the protein dynamics fundamental for the complex role of AMPARs in formation and operation of glutamatergic synapses.