Mauer made his announcement in a letter to fans that was released by the Twins and is set to run in both The Minneapolis Star-Tribune and St. Paul Pioneer Press on Sunday.
"After much consideration I have decided to retire from playing baseball," Mauer wrote in the letter. "The decision came down to my health and my family. The risk of concussion is always there, and I was reminded of that this season after missing over 30 games as a result of diving for a foul ball.
"Thank you, Minnesota Twins, and thank you, fans, for making my career as special and memorable as it was. Because of you I can leave the game I love with a full and grateful heart."
In his 15 major league seasons, Mauer has appeared in six All-Star Games, won three Gold Gloves, three batting titles and racked up 2,123 career hits, all with his hometown Twins.
He is one of 22 former MVPs to play his entire 15-plus-year career with one franchise. Each of the previous 21 is in the Hall of Fame.
The end of Mauer's contract created a natural parting from the game he grew up with in St. Paul, less than 10 miles from the downtown Minneapolis ballparks he called home with the Twins.
The first overall pick in the 2001 draft out of Cretin-Derham Hall High School, the same program that produced Hall of Fame member Paul Molitor, Mauer made his debut at the Metrodome on April 5, 2004, two weeks before his 21st birthday. He signed his megadeal three weeks before the Twins began playing at Target Field.
Mauer acknowledged down the stretch this past season he wasn't sure yet whether he was interested in continuing to play, with twin 5-year-old daughters at home and a third child on the way for him and his wife, Maddie.
Then came the final game of the season on Sept. 30, when he doubled in his last at-bat and donned his catcher's gear to symbolically take one more pitch in the top of the ninth inning as he tearfully waved to the adorning crowd.
What made the moment so emotional was the fact that Mauer had not been behind the plate since Aug. 19, 2013, when a foul tip banged off his mask and triggered a concussion that forced him to move to first base for 2014.
While his athleticism -- he had a scholarship waiting for him to play quarterback at Florida State and was a sharpshooting guard on the basketball team in high school -- allowed for a relatively smooth transition on defense, the effects of the head injury robbed him of his prowess at the plate for most of the next three years.
As a catcher, easily the game's most demanding and dangerous position, Mauer's offensive ability was Hall of Fame-worthy. In 2006, he became the first catcher to lead the league in batting average since 1942. He did so again in 2008 and in 2009, when he hit .365 with a .444 on-base percentage and a .587 slugging percentage to top the American League in all three categories and win the MVP award.
In Mauer's last 10 games as a catcher before the concussion in 2013, he went 17-for-43 with 3 doubles, 3 homers and 9 RBIs.
Staying healthy became a challenge, however, and his popularity lessened some in a state usually fiercely proud of homegrown players due to the size of his contract and the amount of his absences.
A knee injury limited his rookie season to 35 games, and a strained left quadriceps had him on the disabled list for more than a month in 2007. Back trouble sidelined him for all of April in 2009, when Mauer still managed to hit 28 home runs, by far his career high. In 2011, soreness and weakness in both of his legs kept him out for more than two months.
Moving to first base allowed him to play more often, but between 2014 and 2016 his cumulative average was just .267 and the three highest strikeout totals of his career came in each of those seasons.
His renaissance came in 2017 as the Twins went from 59-103 to 85-77 with a spot in the AL wild-card game, and Mauer hit .305 with 36 doubles, the second-highest total of his career.
That made it easy to see Mauer playing beyond 2018, but in the end he opted to walk away with a .306 career batting average, making him one of just two players (Chipper Jones) selected No. 1 overall in the draft to hit over .300 in his career.
Mauer also has a place in the top five on the team's career lists in a clear majority of offensive categories. He is the Twins' all-time leader in doubles and times on base and second in hits behind Kirby Puckett.
The Associated Press contributed to this report.