Opegrapha gyrophorica, O. keyensis and O. protocetrarica, all containing secondary metabolites, are described as new to science from Everglades National Park, Florida, U.S.A. A key is provided for North American species with secondary compounds. In addition, Ampliotrema auratum, Bacidiopsora squamulosula and Eschatogonia prolifera, representing three genera previously unknown from North America, are reported from the mainland of Everglades National Park. Finally, we relate the finding of Coenogonium lutescens, C. pusillum, C. roumeguerianum, C. stenosporum, Graphis paralleloides, G. pyrrhocheiloides and Leucodecton phaeosporum, as new additions to the North American lichen checklist.