Canine parvovirus (CPV) comprises three antigenic variants (2a, 2b, and 2c) with different frequencies and genetic variability among countries. Current CPV populations are considered to be spatially structured with relatively little movement of viruses between geographical areas. Here we describe the evolution and population dynamics of CPV in Uruguay from 2006-2011 using full-length capsid viral protein 2 (VP2) sequences. CPV-2c was the predominant variant in Uruguay for 4 years (2006-2009). The estimated time to the most recent common ancestor suggested that the CPV-2c variant appeared in Uruguay around 2004-2005. Comparative phylogenetic analysis revealed that South American CPV-2c strains did not emerge de novo but may have a European origin. In 2010, a remarkable epidemiological change occurred as a consequence of the emergence of a novel CPV-2a strain in the previously homogeneous CPV-2c population. The frequency of the novel CPV-2a strain increased to 85 % in 2011, representing the first example of a CPV-2a strain replacing a predominant CPV-2c strain in a dog population. The CPV-2a strains detected in 2010-2011 were not phylogenetically related to any other strain collected on the American continent but were identical to Asiatic strains, suggesting that its emergence was a consequence of a migration event. Taken together, our findings suggest that in the last decade, Uruguay has experienced two successive invasions by CPV-2c and CPV-2a variants of European and Asiatic origins, respectively. These results support the hypothesis that CPV invasion events are not rare in certain geographic regions and indicate that some current strains may exhibit an unexpectedly high invasion and replacement capability.