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Simple Summary: The impairment of reproductive and growth performance of pigs by disease is directly connected to the economic loss of a farm. Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the diseases with the highest economic impact prevailing globally. However, the impact of PRRS outbreaks on swine production in South Korea has been rarely reported. By monitoring before and after a PRRS outbreak in a PRRS-negative farm with mass vaccination in sows and gilts, we found that a potential vaccine failure caused by PRRSV infection in this farm caused severe losses in both the farrowing period and growing period, which is similar to or exceeds reports from other countries. As a result, the pig farm in this study suffered extensive production and economic losses due to PRRSV infection, and further studies are needed to estimate the total cost of economic losses due to PRRS outbreaks in the South Korean swine industry. Porcine reproductive and respiratory syndrome (PRRS) is a disease that has inflicted economic losses in the swine industry. The causative agent, porcine reproductive and respiratory syndrome virus (PRRSV), is known to have a high genetic diversity which leads to heterogeneous pathogenicity. To date, the impact of PRRS outbreaks on swine production and the economy of the swine industry in South Korea has been rarely reported. In this study, we compare the reproductive performance in the breeding-farrowing phase and growth performance in the nursery phase, in two 27-week periods, one before and one after a PRRSV1 outbreak on a 650-sow farrow-to-nursery farm caused by a Korean PRRSV1 isolate which was genetically distinct from vaccine strains or other global strains. The reproductive performance of sows and the growth performance of nursery pigs were compared using row data consisting of 1907 mating records, 1648 farrowing records, and 17,129 weaning records from 32 breeding batches. The following variables were significantly different between the pre-PRRS outbreak period and the post-PRRS outbreak period: the farrowing rate (−7.1%, p < 0.0001), the abortion rate (+3.9%, p < 0.0001), the return rate (+2.9%, p = 0.0250), weaning to estrus interval days (+1.9 days, p < 0.0001), total piglets born (−1.2 pigs/litter, p < 0.0001), piglets born alive (−2.2 pigs/litter, p < 0.0001), weaned piglets (−2.7 pigs/litter, p < 0.0001), pre-weaning mortality (+7.4%, p < 0.0001), weaning weight (−0.9 kg/pig, p = 0.0015), the mortality rate (+2.8%, p < 0.0001), average daily gain (−69.8 g/d, p < 0.0001), and the feed conversion ratio (+0.26, p = 0.0036). Economic losses for a period of 27 weeks after a PRRS outbreak were calculated at KRW 99,378 (USD 82.8) per mated female for the breeding-farrowing phase, KRW 8,968 (USD 7.5) per pig for the nursery growth phase, and KRW 245,174 (USD 204.3) per sow in the post-outbreak period. In conclusion, the farrow-to-nursery farm in our study suffered extensive production and economic losses as a result of a PRRSV1 outbreak. [ABSTRACT FROM AUTHOR]