The oxidative carbonylation of ethanol to diethyl carbonate (DEC) has been investigated on catalysts prepared by dispersing CuCl2 and PdCl2 on activated carbon and carbon nanofibers. The objectives of this work were to establish the effects of support structure and pretreatment on the dispersion of the catalytically active components and, in turn, on the activity and selectivity of the catalyst for DEC synthesis. At the same surface loading of CuCl2 and PdCl2, partially oxidized carbon nanofibers resulted in a higher dispersion of the active components and a higher DEC activity than could be achieved on activated carbon. Catalyst characterization revealed that nearly atomic dispersion of CuCl2 and PdCl2 could be achieved on the edges of the graphene sheets comprising the carbon nanofibers. Over oxidation of the edges or their removal by heat treatment of the nanofibers resulted in a loss of catalyst activity. The loss of catalyst activity with time on stream could be overcome by the addition of ppm levels of CCl4 to the feed. While catalysts prepared with CuCl2 alone were active, a fivefold increase in activity was realized by using a PdCl2/CuCl2 ratio of 1/20. It is proposed that the Pd2+ cations interact with [CuCl2]− anions to form Pd[CuCl2]2 complexes that are stabilized through dative bonds formed with oxygen groups present at the edges of the graphene sheets of the support. A mechanism for DEC synthesis is discussed, and a role for the Pd2+ cations as part of this mechanism is proposed.