Miocic trains out of Strong Style Fight Team in Ohio along with UFC veteran Forrest Petz and Bellator's Chris Lozano and Brian Rogers. He received interest from Major League Baseball teams during his collegiate years at Cleveland State University and ranked nationally in wrestling at 197 lbs alongside such names as Nik Fekete, Ryan Bader, and Muhammed Lawal. Miocic played baseball his senior year at Trevecca Nazarene University in Nashville, Tennessee.He helped lead the team to the TranSouth Athletic Conference regular season and tournament championship, hitting .344 with 14 doubles, 4 triples, 7 home runs and 43 RBI. He earned the TranSouth Player of the Week award. Miocic is also a former Golden Gloves champion and NCAA D1 wrestler.

Miocic would win his first 5 MMA bouts by TKO earning him a heavyweight title shot for NAAFS. He would beat Bob "Zombie" Brents to win the title by submission after he hit him with numerous leg kicks.

Miocic made his UFC debut against Joey Beltran on October 8, 2011 at UFC 136 and won the fight via unanimous decision. He would follow up his debut with a Knockout of the Night over Phil De Fries and another TKO win over Shane Del Rosario. Stipe would face off against Stefan Struve in the Main Event of UFC on Fuel TV 5. Miocic would lose by TKO in the second round however he did earn Fight of the Night. After the TKO loss to Struve, Miocic would bounce back in a huge way at UFC 161 with his greatest victory to date, upsetting top HW contender and TUF season 10 winner Roy "Big Country" Nelson. Miocic not only shocked the world with that victory, but he also showcased a wealth of improvement in his overall striking both defensively and offensively.

Miocic then faced another heavy hitter in the Brazilian Jiu-Jitsu Black Belt Gabriel Gonzaga, owner of 11 devastating finishes in the UFC Heavyweight division both by submission and T/KO. After a slow and rather tedious first round in which Miocic mostly tried to avoid and block Gonzaga's heavy strikes, the young boxer took over early in the second round, scoring with multiple punches, stuffing all of Gonzaga's takedowns and getting a knockdown of his own en-route to a comfortable Unanimous Decision victory.

Next Miocic faced Fábio Maldonado, a fighter who normally fights at Light Heavyweight known for his ability to absorb a lot of damage, and knocked him out in only 0:35 seconds. Miocic then went on to headline UFC on Fox 13 against Junior dos Santos where he lost a close decision. Following his loss Miocic headlined another card UFC Fight Night 65 on May 10th 2015 where he fought against Mark Hunt where he pummeled Hunt for 4 rounds before finally finishing him in the 5th round. Then Miocic fought Andrei Arlovski who was on a 6 fight win streak. Miocic beat Arlovski by TKO in under a minute and earned himself a title shot against Fabrício Werdum at UFC 198. Miocic tried to press Werdum causing him to come forward punching at Miocic. While moving backward Miocic threw a right hook that crumples Werdum. Miocic becomes the Heavyweight champion by first round KO.