The team announced early on Tuesday in a press release that Garfinkel, who had been with the team since 2009, had resigned.
The press release indicated that lead investor Peter Seidler and executive chairman Ron Fowler accepted the resignation.
"I want to thank the Padres and the fans for the opportunity to be a small part of this incredible franchise and America's Finest City," Garfinkel said by email Tuesday. "I have a lot of faith in the people in this organization and that great things are on the horizon."
According to a source with knowledge of the situation, Garfinkel's decision to resign was part of the transition to the new ownership group and that there was no acrimony on either side.
The press release indicated that Seidler and Fowler thanked Garfinkel for "Tom's many contributions to the Padres over the last four years."
Fowler didn't respond to a request for comment on Garfinkel's resignation.
San Diego manager Bud Black was asked about Garfinkel's resignation before Tuesday's game against the Rockies.
"Our focus down here is the team, but he was very visible," Black said. "He was around, he was always asking what he can do for the club, for the players. He made an impact. He was a very creative, very progressive thinker and he'll be missed obviously, but he'll land on his feet and do great things."
Garfinkel said Tuesday that he's doesn't have any current job offers.
Garfinkel was named president and COO of the Padres in April of 2009 and was later promoted to CEO in April of 2012. He was brought to San Diego by former Padres vice chairman and CEO Jeff Moorad. Those two previously worked together with the D-backs.
In March of 2012, Moorad withdrew his application to complete the sale of the team. A month later, the team was up for sale again.
The organization has been under new ownership since August when the team announced it had been purchased by the Seidler/O'Malley group and Fowler for $800 million from former majority owner John Moores.
Fowler will assume Garfinkel's responsibilities on an interim basis until a new president and CEO can be hired.
Since joining the Padres, Garfinkel pushed for a better ballpark experience at Petco Park and raising the team's season-ticket base. He was also instrumental in helping the team broker a television deal worth $1.2 billion over 20 years with Fox Sports San Diego.
In 2011 and 2012, the Padres were recognized in a SportsBusiness Journal survey for having the No. 1 ticket sales and service team in baseball.
One of Garfinkel's lasting legacies with the Padres will likely be the Youth Baseball Initiative, where the organization fitted more than 11,600 local Little Leaguers -- and more than 850 teams -- with authentic, custom-made jerseys from throughout Padres history, as well as corresponding caps.
"No one cared more about the Padres and bringing the fans a winner than Tom," said Brent Stehlik, the Padres former senior vice president of business operations of the Padres. "No one cared more about improving the fan experience -- every facet, from food to audio to membership program -- than Tom.
"No one wanted to impact the community more than Tom, evident by the greatly expanded military recognition and little league jersey initiative. No one has been more influential to my career. I can't say that I have learned more from anyone else through all my stops in sports."
Stehlik is currently the chief revenue officer for the Cleveland Browns.
In April, Garfinkel apologized for comments that he made connecting Dodgers' pitcher Zach Greinke's social anxiety disorder to a movie character who suffered from autism during a talk with season-ticket holders.
The comment was made after Greinke hit Padres' left fielder Carlos Quentin with a pitch in a game at Petco Park, which sparked a benches-clearing incident.