Bench coach Rod Barajas will serve as the team's interim skipper for the rest of the season.
Green had held the managerial role since 2016 and has two years left on his contract after receiving an extension in 2017. The Padres went 274-366 with Green at the helm.
"I want to thank Andy for his tireless work and dedication to the Padres over the last four seasons," executive vice president and general manager A.J. Preller said. "This was an incredibly difficult decision, but one we felt was necessary at this time to take our organization to the next level and expedite the process of bringing a championship to San Diego.
"Our search for a new manager will begin immediately."
Former major-leaguer Moises Alou is viewed as a strong candidate to be the team's next manager, if he wants the job, Jon Morosi of MLB Network reports.
The Padres were expected by many to take a step forward in 2019 but have failed to live up to expectations. The club sports a 69-85 record despite signing four-time All-Star Manny Machado to a monster 10-year deal in March and blue-chip prospects like Fernando Tatis Jr. and Chris Paddack turning into stars.
San Diego sits fourth in the NL West and hasn't made the playoffs since 2006.