Filarial nematodes of theDipetalonemalineage are widespread parasites and include some species that are transmitted by ticks. In this study, we conducted a large molecular survey of ticks in French Guiana, South America, to understand the overall diversity of tick-borne filarioids in this remote region largely covered by dense tropical forests. Out of 682 ticks belonging to 22 species and 6 genera, 21 ticks (3.1%) of the speciesAmblyomma cajennense,A. oblongoguttatum,A. romitii,Ixodes luciaeandRhipicephalus sanguineus sensu latowere positive for infection by filarioids. Molecular typing and phylogenetic analysis identified all these filarioids as members of theDipetalonemalineage. While the filarioid ofR. sanguineus sensu latois a previously described species, the canine wormCercopithifilaria bainaeAlmeida & Vicente, 1984, all other filarioids detected in this study are related but distinct to already known species in the generaCercopithifilaria,CruorifilariaandDipetalonema. Their vertebrate host range may include a wide variety of mammals present in French Guiana, but dogs, capybaras, and opossums are the best candidate hosts for some of these filarioids. Although the detection of members of theDipetalonemalineage in ticks of significant medical or veterinary interest is of concern, the risk of contracting a tick-borne filarial infection is still largely unknown. The pathogenicity of these filarioids, their epidemiology, developmental cycles, and mechanisms of transmission by South American tick species now require further study.