A native of Sharon, Wisconsin, Frederick attended Big Foot High School in Walworth, Wisconsin, where he was an all-state two-way lineman. He helped his high school team to second place in the 2008 WIAA Division 4 state playoffs.

In order to preserve a year of Frederick’s NCAA eligibility, Wisconsin coaching staff decided to redshirt him in 2010. In his redshirt sophomore season, Frederick replaced John Moffitt, starting 11 of 13 games at left guard. For two games, he had to substitute for Peter Konz at center.

In the 2013 NFL Draft, the Dallas Cowboys traded down in the first round with the San Francisco 49ers in exchange for a third-round pick (used to draft Terrance Williams). In the first round, the team selected Frederick after eight offensive linemen were drafted before him. This decision caused a stir in the media because it was not only seen as a reach, but the trade was also criticized for bringing poor compensation after moving down 13 positions.

In 2015, he had to work with four different starting quarterbacks with varying degrees of knowledge of the team’s offense, which required him to make more protection calls. He was named to his second Pro Bowl.

On August 13, 2016, Frederick signed a six-year, $56.4 million contract extension with the Cowboys, making him the highest-paid center in the league.

On December 19, 2017, Frederick was named to his fourth straight Pro Bowl alongside tackle Tyron Smith and guard Zack Martin for the second straight year.

On September 3, 2018, Frederick was not placed on injured reserve to start the 2018 season after being diagnosed with Guillain–Barré syndrome on August 22. He was inactive for the first four games before inevitably being placed on the reserve/non-football illness list on October 6, 2018.

On August 22, 2018, Frederick was diagnosed with Guillain–Barré syndrome.

On March 23, 2020, Frederick announced his retirement from professional football.