Žižić's first team was KK Split, in the 2013–14 season, but he played for their junior team, in which he only played in 3 games. He then moved to the Cedevita Zagreb's junior team, and with them he played in 5 games.
Gorica (2014)
To start the 2014–15 season, Žižić played for Gorica.
Cibona (2014–2016)
Žižiće moved to Cibona Zagreb for the rest of the season. In that year, he averaged 7.4 points, 0.3 assists, 0.3 steals, and 0.9 blocks, in 15.5 minutes per game, in 25 games played in the Adriatic League. His breakout season was in the 2015–16 season.
On 11 October 2016, Žižić was named the MVP of the fourth week of the 2016–17 ABA League season. He scored 37 points and grabbed 20 rebounds in Cibona's 89–85 win over MZT Skopje Aerodrom, in a game that was decided after double overtime.[3]
With Darüşşafaka, Žižić made his debut in the European top-tier level, the EuroLeague, on 30 December 2016, in an 81–77 road loss against FC Barcelona. In his first EuroLeague game, Žižić had 4 points, 6 rebounds, 2 steals, and 2 blocks.[5]
On 1 July 2017, Žižić signed with the Boston Celtics.[7] Before even suiting up for a single regular-season game for the Celtics, Žižić was traded to the Cleveland Cavaliers alongside Isaiah Thomas, Jae Crowder, and the Brooklyn Nets' unprotected 2018 first-round pick for Kyrie Irving on 22 August 2017.[8] However, eight days after the trade was first confirmed, the Celtics would also add a 2020 second-round pick from the Miami Heat in order to fully complete the deal to satisfy Cleveland's worries involving Thomas's hip injury.[9]
Žižić spent time with the Canton Charge during his rookie season. On 11 March, he scored 15 points and recorded 7 rebounds (both career highs) in a loss to Los Angeles Lakers. In the last game of the regular season, he scored 20 points and recorded 7 rebounds. The Cavaliers made it to the 2018 NBA Finals, but lost the series 4–0 to the Golden State Warriors.
Maccabi Tel Aviv (2020–2022)
On 25 August 2020, Žižić signed a two-year deal with Israeli team Maccabi Tel Aviv.[10] In 2020–21, he led the league with a .699 field goal percentage, and was 10th in the Euroleague with 0.8 blocks per game.[11][12]
On 9 May 2022, during a game against Hapoel Haifa, Žižić lost consciousness after hitting his head on the ground. He was rushed to a hospital and regained consciousness later that night.[13][14]
On 21 June 2022, Žižić officially parted ways with the Israeli club after two seasons.[15]
Anadolu Efes (2022–2023)
On 22 June 2022, Žižić signed a three-year (2+1) contract with Turkish club Anadolu Efes, the reigning back-to-back EuroLeague champions.[16]
Virtus Bologna (2023–present)
On 31 December 2023, Žižić signed a two-year contract with Italian powerhouse Virtus Bologna.[17]