Hoyer becomes the 15th general manager in club history and succeeds interim GM Randy Bush, who took over for Jim Hendry in July.
He takes over a Cubs team which stumbled to a 71-91 record in 2011, on the heels of a 75-87 finish in 2010. Chicago made back-to-back playoff appearances in 2007 and 2008, then went 83-79 in 2009.
Hoyer, along with Jason McLeod -- who was named senior vice president of scouting and player development -- come from the San Diego Padres, where both men held similar posts.
"Jed and Jason are among the most dynamic in the game and both will have a significant impact on our baseball operations department," said new Cubs president of baseball operations Theo Epstein. "I've worked with both extensively in the past and am excited to build an organization with them again."
The 37-year-old Hoyer spent the last two seasons as San Diego's GM, following eight seasons with the Boston Red Sox, where he worked with Epstein and finished his tenure as the club's senior VP and assistant general manager.
Hoyer aided Boston's ascent by taking an active role in scouting and player development, helping turn the franchise into one which compiled four ALCS appearances and a pair of World Series titles (2004, 2007).
Over his two years at the helm, the Padres finished 161-163. A 90-72 record in 2010 was followed by a 71-91 mark this past season.
McLeod, 39, spent 10 seasons with the Padres (1994-2003), rising through the ranks to become assistant director of scouting. He then joined the Red Sox for the 2004 season and remained through 2009, leaving for San Diego when Hoyer was named GM there.