Foot-and-mouth disease (FMD) is a persistent, major economic concern for livestock productivity, which is highly exacerbated by outbreaks in Thailand. FMD virus (FMDV) serotype A is more highly antigenic and genetically diverse than other serotypes, which has important implications for vaccine development as well as selection. Therefore, it is essential to continuously monitor antigenic and genetic changes of field isolates of FMDV serotype A. Here we used antisera against three vaccine strains (A/118/87, A/Sakolnakorn/97, and A/Lopburi/2012) to analyze the antigenicity of 133 field isolates of FMDV serotypes A in Thailand from 2007 to 2019. The majority of the isolates from 2007 to 2008 reacted only with the antiserum against strain A/118/87. In contrast, antigenic analysis revealed broad cross-reactivity and antigenic variations of the isolates from 2009 through 2019 against strains A/Sakolnakorn/97 and A/Lopburi/2012. These results indicate periodic changes in the antigenicity of field isolates of FMDV serotype A. Phylogenetic analysis of the VP1 region revealed that all isolates were of the Sea-97 lineage within the ASIA topotype. Analysis of the L-fragment genome sequences of 30 FMDV isolates collected throughout Thailand revealed highly variable amino acid sequences of VP1 and 3A, with the lowest average identity (94.56%) and invariant (78.43%) rates, respectively. The present findings indicate the importance of an active routine surveillance system incorporating antigenic and genetic analysis designated to continually update information about field isolates of FMDV serotype A. Such a system is essential for establishing and improving measures to control FMDV infections in Thailand and in neighboring Asian countries.