On July 29, 2005, he was traded by the Rangers to the San Diego Padres in exchange for Phil Nevin. Padres fans had hoped that Park could repeat his previous success by playing in pitcher-friendly Petco Park.
In the 2005 season, his combined record was 12-8, despite a 5.74 ERA. In the 2006 season, Park was reunited with his former Texas Rangers teammate and friend Chris Young, who was traded to the Padres in exchange for Akinori Otsuka. Park started the season as a reliever but soon he became a starter. On July 31, he suffered from intestinal bleeding and was placed on the disabled list. Several of his teammates, including Jake Peavy, Woody Williams, Chris Young, and Alan Embree, offered to donate their blood, but Park graciously refused their offer, as they were vital members of the team. Park accepted blood transfusions, that came, in part, from Jake Peavy's wife Katie and Kelly Calabrese, Padres' team massage therapist. However, Park's recovery did not last long as he suffered from another episode of intestinal bleeding on August 21. He was hospitalized again, this time along with his wife Rie, who was about to deliver their first child. A very thorough medical examination revealed that Park was suffering from a congenital defect called Meckel's diverticulum. Park had a successful surgery and only six days later his wife delivered a healthy baby daughter at the same hospital.
Between the 2005 season and the 2006 season, Park represented South Korea in the World Baseball Classic. In the Asia Round games against Taiwan and Japan, Park made appearances as a closing pitcher, shutting out the opposing lineups. He made another appearance as a closer in the semifinal game against Mexico, in which he again shut out his opposing hitters. His performance made San Diego Padres' manager Bruce Bochy believe that Park can be used as an effective reliever as well as a starter. Park later said that Padres' closer Trevor Hoffman taught him how to focus in a relief situation. With his shutout performance in 10 innings and three saves, Korea finished the World Baseball Classic in third place and Park was selected to the WBC All-Star team along with his teammate Lee Seung-yeop and Team Korea's captain Lee Jong-beom.
Park married Korean-Japanese socialite Ri-hye Park on November 29, 2005. An ethnic Korean, she grew up in Japan and went to culinary school in New York. She is publicly known as a semi-professional chef, writer and the only daughter of Japan's 76th richest man according to The Philadelphia Inquirer. In spring 2009, Ri-hye released a best-selling cookbook in South Korea whose proceeds went to children's charities on behalf of the Chan Ho Park Dream Foundation. Park and his wife have three daughters.