The six-time All-Star selection has not played this season after becoming a free agent when the Brewers declined to exercise a $15 million mutual option in his contract last October.
"I have weighed this decision for many months," Braun, 37, said in a video posted to social media by the Brewers. "While I still love this game very much, the time is right for me to retire from my playing days.
"It's difficult to describe my emotions today, but it starts with overwhelming gratitude to those who have shared this experience with me while offering their unconditional support at every turn. ... I will forever appreciate the best fans in the game and the countless people who came out to the ballpark night after night, making Milwaukee the greatest city to play the game."
In addition to his 352 home runs, Braun, who played all 14 of his MLB seasons with the Brewers, ranks second in franchise history in career RBIs (1,154), extra-base hits (809), total bases (3,525) and doubles (408). He ranks third in runs (1,080), hits (1,963), triples (49), stolen bases (216) and walks (586).
"I am so fortunate to have enjoyed a 14-year career wearing the jersey of one team, and even more grateful that team is the Milwaukee Brewers," Braun said. "I am retiring today from Major League Baseball, but my love for all those who supported me continues to grow. I cherish great memories from my time with the Brewers and will continue to build on the many friendships made in this amazing city."
Braun batted a career-low .233 in 2020 with seven homers and 27 RBIs in 39 games while dealing with a back issue. He came on strong late in the season and had a .958 OPS in September.
His back issues prevented him from playing in the Brewers' first-round playoff loss to the eventual World Series-champion Los Angeles Dodgers.
Braun was one of baseball's best hitters from 2007 to 2012, but was never the same after he was suspended midway through the 2013 season for using performance-enhancing drugs. He acknowledged that he took banned substances while rehabilitating an injury and apologized.
From 2014 on, Braun never played more than 144 games in a season and reached the 30-homer mark once after topping 30 homers five times in his first six years, including an NL-leading 41 in 2012. Still, he remained a key contributor for the Brewers.
"I always thought that the way Ryan's last six or seven years went, he should be incredibly proud with how those years went," Brewers manager Craig Counsell said. "He should be incredibly proud of that. At that point, he had a story to write. He didn't know how it was going to go, and I think he wrote a great story and that he should be proud of that."
Braun was teammates with Counsell early in his career before eventually playing for him.
"What I always tell Ryan is, I always joke with him that, 'Maybe besides your mom and your dad, I have seen you play baseball probably more than anyone in the world.' I was there for every game throughout his career," Counsell said. "I got a close seat for a vast majority of them. Watching him play was definitely an honor."
The Brewers selected Braun with the fifth overall pick in the 2005 amateur draft out of Miami. He was named NL Rookie of the Year in 2007 and ranked in the top 15 in the MVP voting every year from 2008 to 2012. He finished second in the MVP balloting in 2012 and third in 2008.
"Ryan brought us many unforgettable moments on the field; from playoff-clinching, dramatic home runs to nearly 2,000 career hits, he is unquestionably one of the greatest players in Brewers history," team chairman Mark Attanasio said in a statement.
The Brewers will honor Braun with an on-field ceremony on Sept. 26.
"It's well-deserved considering what he's done for the city, the organization and obviously, [after] not having a chance to play in front of fans last year, to get that sendoff," outfielder Christian Yelich said.
The Associated Press contributed to this report.