He played college football for the Ohio State Buckeyes and was selected by the Steelers in the first round of the 2014 NFL draft.

During the 2017 season, in a game against the Cincinnati Bengals, Shazier attempted to make a head-first tackle that left him a paraplegic, after which he had to have spinal stabilization surgery and learn to walk again.

He received numerous positive reviews for his athleticism, agility, production, flexibility, acceleration, strong hands, and lateral movement.

Most negative reviews by analysts were based on his lack of ideal size and his under developed vision, instincts, anticipation, and awareness.

He made his professional regular season debut and first career start in the Steelers' home opener against the Cleveland Browns.

In his first career playoff game, Shazier made 3 solo tackles and one assist in a 17–30 wild-card loss to the Baltimore Ravens.

[13] On January 9, 2016, during the AFC Wildcard game against the Cincinnati Bengals, Shazier stripped the ball from Jeremy Hill with 1:36 left in the fourth quarter.

[15] He made his return in a Week 7 matchup against the New England Patriots and was limited to two assisted tackles and a pass deflection in the 27–16 loss.

[13] On November 20, 2016, Shazier racked up seven total tackles, a pass deflection, and sacked Josh McCown for his first of the season, as the Steelers defeated the Cleveland Browns 24–9.

[16] On December 25, 2016, he recorded ten combined tackles and intercepted Joe Flacco in a 31–27 playoff clinching victory over the Baltimore Ravens.

The next game, Shazier made eight combined tackles and intercepted Robert Griffin III in a 27–24 win over the Browns on their season finale.

[13] On January 8, 2017, Shazier recorded six combined tackles and intercepted Matt Moore, as the Steelers defeated the Miami Dolphins in the AFC Wildcard game 30–12.

[17] On January 15, 2017, he recorded 5 combined tackles and intercepted Alex Smith in the Steelers' 18–16 Divisional Round victory over the Kansas City Chiefs.

[13] During a Monday Night Football game against the Bengals on December 4, 2017, Shazier sustained what appeared to be a severe back injury after a head-on tackle.

[19] On December 7, Shazier underwent spinal stabilization surgery to secure the injured section of spine and to aid in his recovery.

[25] On April 26, 2018, Shazier walked onto the AT&T Stadium stage with his fiancée, Michelle Rodriguez, to announce the 28th pick of the NFL draft, Terrell Edmunds.

[27] On November 30, 2018, Shazier jogged for the first time since his spinal stabilization surgery, according to Steelers linebacker coach Joey Porter.

Seventeen months after suffering the spinal injury that doctors feared would leave him paralyzed, Shazier was able to dance at his wedding.

[40] In the fall of 2019, Shazier returned to college, and graduated in December 2020 at his alma mater, Ohio State University.