Weaver spent 11 seasons with the Angels before joining the San Diego Padres in February. The 34-year-old recorded an 0-5 mark with a 7.44 ERA in nine starts with the Padres before sitting out the last three months with an inflamed left hip.
"I've decided to step away from baseball," Weaver said in a statement released on Twitter. "While I've been working hard to get back on the mound, my body just will not allow me to compete like I want to. Many thanks to the Padres' organization for the opportunity to play in the amazing city of San Diego. You have been very professional and respectful during this process, and I really appreciate that.
"I would also like to thank my teammates for welcoming me in with open arms and for all the support throughout the season. I'm excited for the next chapter in life and making up for lost time with my family. Thank you to everyone who has supported me over the years. It was a great ride."
Weaver's career hit its high note from 2010-12, as he finished in the top five in American League Cy Young Award voting in each season. He led the majors with 233 strikeouts and 34 starts in 2010 and notched 18- and 20-win campaigns in each of the following years.
Weaver tossed the 10th no-hitter in Angels history on May 2, 2012.
Weaver finished his career with a 150-98 record and a 3.63 ERA. The No. 12 overall pick in the 2004 draft, Weaver guided an Angels team that won three straight AL West division titles from 2007-09. He is second in Angels franchise history in wins and games started (322) and is third in innings pitched (2,025) and strikeouts (1,598).
"Over the past decade, Jered established himself as one of the premier pitchers and fiercest competitors in baseball," Padres general manager A.J. Preller said in a statement. "He built a tremendous reputation throughout the game, not only for his track record of success, but also as a consummate teammate and professional. On behalf of the Padres' organization, I want to congratulate Jered on an outstanding career."