Recombination of rapidly evolving RNA-viruses provides an important mechanism for diversification, spread, and emergence of new variants with enhanced fitness. Foot-and-mouth disease virus (FMDV) causes an important transboundary disease of livestock that is endemic to most countries in Asia and Africa. Maintenance and spread of FMDV are driven by periods of dominance of specific viral lineages. Current understanding of the molecular epidemiology of FMDV lineages is generally based on the phylogenetic relationship of the capsid-encoding genes, with less attention to the process of recombination and evolution of non-structural proteins. In this study, the putative recombination breakpoints of FMDVs endemic to Southeast Asia were determined using full-open reading frame sequences. Subsequently, the lineages' divergence times of recombination-free genome regions were estimated. These analyses revealed a close relationship between two of the earliest endemic viral lineages that appear unrelated when only considering the phylogeny of their capsid proteins. Contrastingly, one lineage, named O/CATHAY, known for having a particular host predilection (pigs) has evolved independently. Additionally, intra-lineage recombination occurred at different breakpoints compared to the inter-lineage process. These results provide new insights about FMDV recombination patterns and the evolutionary interdependence of FMDV serotypes and lineages. Foot-and-mouth disease (FMD) is one of the most important diseases of livestock worldwide 1,2. Many countries with endemic FMD have rural populations that are highly reliant on their livestock as critical assets. The causal agent, FMD virus (FMDV), affects cloven-hoofed animals and is endemic in all countries in mainland Southeast Asia, where clinical cases are regularly observed in livestock, including pigs, cattle, Asian buffalo and small ruminants. FMDV belongs to the genus Aphthovirus of the family Picornaviridae and has a single-stranded, positive-sense, non-segmented RNA genome consisting of an open reading frame (ORF) region of ~7000 nucleotides (nt). The genome encodes for a single polyprotein that is post-translationally processed into 4 capsid proteins (VP1-4) and 10 non-structural proteins (NSP; leader proteinase (L pro), 2A, 2B, 2C, 3A, 3B1 VPg1 , 3B2 VPg2 , 3B3 VPg3 , 3C pro and 3D pol), bounded by 5′and 3′untranslated regions (UTRs) 3. FMDV has been classified into seven distinct serotypes, namely A, O, C, Asia-1, Southern African Territories (SAT) 1, SAT 2 and SAT 3 4 , many of which exist as multiple strains or lineages circulating in endemic regions 5 .