Mack joins the 49ers after five NFL seasons with the Atlanta Falcons, having originally been drafted by the Cleveland Browns in the first round in 2009.
The 35-year-old spent his first seven seasons in Cleveland before signing a five-year, $57.5million contract in Atlanta before the 2015-16 campaign.
"The 49ers, obviously there's a connection with Kyle Shanahan, and him as a head coach and the offense he runs, that always has been something that I know it's a system I can be really good in," Mack said on Thursday.
"It's an offense I know I can excel at, so it was a very good fit between a good team and a good spot with a good coaching staff and a place I can be a good player in."
"We are excited to add another Pro Bowl player to our offensive line," 49ers general ,anager John Lynch said.
"Throughout his career, Alex has been a model of consistency. His leadership and high character will be felt throughout our team and community."
Mack, who grew up in California, has had a decorated career, as a three-time Second-Team All Pro (2013, 2016 and 2017) and being named in the NFL's 2010s All-Decade Team.
He made 90 consecutive regular-season starts until a concussion in the 2020 season ended that run.
The 49ers missed the NFL playoffs in 2020, finishing with a 6-10 record under head coach Kyle Shanahan, who remains in charge.
San Francisco have already added cornerbacks Mark Fields and Briean Boddy-Calhoun and tight end Daniel Helm this off-season.
Chosen as a member of the Pro Football Hall of Fame's All-Decade Team of the 2010s, Mack started 196 career games for the Cleveland Browns, Atlanta Falcons and – most recently – the San Francisco 49ers.
"I am so grateful to the game of football and everything it has given me," Mack said in a statement on Twitter. "From the very start it helped shape who I am and taught me life lessons. I started to play football because it was fun and that never changed."
Mack was a first-round draft pick in 2009, selected 21st overall by Cleveland, where he earned All-Rookie honours after starting 16 games in his first season as a professional.
Mack played seven seasons with the Browns and was named an Associated Press Second-Team All-Pro in 2013. He received the honour twice more in 2016 and 2017, playing for the Falcons.
Mack played in eight career playoff games, including Super Bowl LI, in which the New England Patriots famously rallied from a 25-point deficit to beat the Falcons in overtime.
A native of Santa Barbara, California, and graduate of the University of California, Mack returned to his home state to play his final pro season with San Francisco, helping the 49ers to the NFC Championship game.
"We would like to thank Alex for all that he brought to the 49ers throughout the 2021 season," 49ers general manager John Lynch said in a statement.
"The center position in the NFL is the heartbeat of an offense and Alex's intellect, consistency, love for the game and professional approach made a lasting impression over the course of his 13 NFL seasons."
