We have sequenced a large plasmid that occurs among avian pathogenic Escherichia coli isolates. This plasmid, pAPEC-O1-R, is a 241,387-bp IncHI2 plasmid which is cotransmissible via bacterial conjugation with a ColBM virulence plasmid, encodes resistance to eight antimicrobial agents, and appears to occur at low rates among extraintestinal E. coli isolates.