A youth product at Partizan, he turned professional after a loan at Teleoptik, and was a regular as they won the Serbian SuperLiga in his first season. He then joined Anderlecht for a club record €5 million, and scored 44 goals in 90 games across all competitions in a two-season spell. He won the Belgian Pro League in his first campaign at the club, and was the league's top scorer in his second. In 2015, he moved to Newcastle United for £13 million.
Mitrović helped Serbia win the 2013 European Under-19 Championship, being voted the best player of the tournament. Since that year, he has also been a senior international player, earning over 20 caps.
Born in Smederevo, Mitrović came to Partizan and went through the youth system of the club. Before being promoted to the first team, he made his senior debut with their affiliated side Teleoptik in the 2011–12 season, scoring seven goals in 25 league matches.
On 27 June 2012, together with two Teleoptik teammates, Mitrović signed his first professional contract with Partizan, on a four-year deal. He made his official debut for the club in a Champions League qualifier against Maltese side Valletta, scoring a goal nine minutes after coming on as a substitute. On 23 August 2012, Mitrović scored a header against Tromsø in the Europa League play-off round. Three days later, he scored his first league goal in a home fixture against Jagodina. On 17 November 2012, Mitrović scored the opening goal in his first ever Eternal derby, which Partizan eventually lost 3–2. Five days later, he also scored in a 1–1 away draw with Azerbaijani side Neftchi Baku during the Europa League group stage. By the end of his debut season, Mitrović was Partizan's top scorer in all competitions with 15 goals in 36 appearances even though he was one of the youngest players of the team. Due to his displays, he earned a place in Jelen SuperLiga's Team of the Season selection. Additionally, Serbian sports portal Mozzart Sport rated Mitrović third of 25 best players in the national league for that season.
On 12 August 2013, after much speculation, it was announced that Mitrović was sold to Anderlecht and that he would join the Belgian club on 30 August at the request of the player and his family. The transfer fee was €5 million, which is Anderlecht's record signing fee. On 1 September, Mitrović provided two assists on his debut for the club after coming on as a substitute at the beginning of the second half in a league match against Zulte Waregem.
On 10 December 2013, in the last round of the Champions League Group C against Olympiacos, Mitrović replaced goalkeeper Silvio Proto who had been sent off, but failed to save a penalty from Alejandro Domínguez.
Mitrović ended his debut season in Belgium with 16 league goals as Anderlecht won their 33rd league title.
Mitrović began the 2014–15 season by scoring in Anderlecht's 2–1 Super Cup defeat of K.S.C. Lokeren. On 5 November 2014, he scored an equalizing goal in the 90th minute in the UEFA Champions League versus Arsenal, completing Anderlecht's comeback from 3–0 to 3–3. Overall, he scored 20 goals in the Pro League, making him the competition's top scorer, and 28 in all competitions. On 22 March 2015, he scored the team's only goal in the 2–1 Belgian Cup Final loss to Club Brugge KV in Brussels.
On 21 July 2015, Mitrović joined Newcastle United on a five-year deal for a reported £13 million, saying he hoped to be able to play like club legend Alan Shearer. He made his debut on 9 August as Newcastle began the season with a 2–2 draw against Southampton at St James' Park, playing the final 15 minutes in place of Papiss Cissé. He was booked 22 seconds into his debut for a foul on Matt Targett. Twenty days later, he was sent off in the 15th minute of a 0–1 home defeat to Arsenal for a foul on Francis Coquelin.
Mitrović scored his first Newcastle goal on 3 October away to Manchester City, opening the scoring in a 6–1 loss. In his next game, he netted the fourth goal in the team's first win of the season, a 6–2 home thrashing of Norwich City. He scored his third goal on 13 December in an away game against Tottenham Hotspur, equalising in a 1–2 win two minutes after coming on as a substitute for Cissé.
He won and converted a penalty in a 3–3 draw against Manchester United on 12 January 2016. On 20 March, he headed the equaliser in a 1–1 draw against arch-rivals Sunderland in the Tyne–Wear derby. Mitrović was booked for taking off his shirt in celebration, and a fan who ran onto the pitch to celebrate with him was given a banning order.
On 2 April, Mitrović scored two goals, one from a penalty, in a 3–2 defeat to Norwich City. On the final day of the season, and with Newcastle United already relegated, Mitrović scored the second goal in a 5–1 win over third-place Tottenham Hotspur, but was also sent off for a shin-high challenge on Kyle Walker. He is the sixth player in Premier League history to score a goal, assist a goal and get sent off in the same match.
After being suspended for the first four matches of the season as punishment for his red card against Tottenham Hotspur at the end of the previous season, Mitrović made his season debut in the EFL Cup against Cheltenham on 23 August, but was forced off with a head injury in the first half. As a result, Mitrović had to wait until 13 September to make his Championship debut, scoring his first goal of the 2016–17 season at Queens Park Rangers, with the fifth goal in a 6–0 win. On 25 October, he bagged a brace and an assist in a 6–0 win over Preston North End, as the Magpies advanced to the EFL Cup quarter-finals. That weekend, Mitrović received his first league start since the match at Loftus Road, and against the same opposition, Mitrović again scored a brace in a 2–1 win. Despite losing playing time to summer signing Dwight Gayle, Mitrović remained positive, saying "maybe last season I played more, but we are in good shape", as Newcastle arrived at the top of the table on 18 October.
On 7 January 2017, Mitrović started the FA Cup third round match against Birmingham City, but was injured in the buildup to the opening goal, scored by Daryl Murphy. On 11 February, Mitrović scored the only goal in a win over Wolverhampton Wanderers. However, he was substituted at half-time as a precaution, as he had been booked earlier in the match and could have been sent off for a challenge on Carl Ikeme.
On 23 August, Mitrović scored the first goal of the 2016–17 season, opening the scoring in what would be a eventual extra-time loss to Nottingham Forest in the EFL Cup. Three days later, Mitrović netted again with the third goal in a 3–0 win over West Ham United. On 30 August, he was suspended for three matches, after an elbow to the head of Manuel Lanzini was picked up by television cameras.
With four goals, Mitrović was the top scorer of the Serbian national under-19 team in their successful qualifying campaign for the 2012 UEFA Under-19 Championship. On 3 July 2012, the opening day of the final tournament, he was sent off during a match against France U19, which caused him to miss the rest of the competition due to suspension. On 26 March 2013, Mitrović scored two goals in a friendly for Serbia's U21 team against Bulgaria U21.
Mitrović was called up by Serbia's U19 coach Ljubinko Drulović for two qualification matches for the 2013 UEFA Under-19 Championship taking place after his debut with the senior national side against Belgium. Mitrović was also a member of the squad that traveled to Lithuania for the final tournament, where he established himself as one of the key players in Serbia's U19 team which won the competition for the first time in the history of Serbian football. He contributed by scoring a goal and providing two assists during the contest (including one in the final match against France U19. Also, Mitrović was named the tournament's Golden Player for his performances.
Mitrović earned his first call up to the Serbian senior national team by coach Siniša Mihajlović for a 2014 FIFA World Cup qualifier against Belgium. He played 69 minutes on his debut on 7 June 2013 and earned a yellow card after stepping on Axel Witsel's foot, before being substituted for Marko Šćepović. On 6 September, Mitrović scored his first goal for the senior side in a 1–1 home draw against Croatia in another World Cup qualifier. Two years and a day later, he scored his next international goal, the consolation in a 2–1 friendly defeat to France at the Nouveau Stade de Bordeaux, Serbia's 100th match as an independent nation.
In the 2018 FIFA World Cup qualifiers, Mitrović scored three goals in two matches to ensure Serbia were still in contention to qualify from their group. On 9 October 2016, he scored a brace in a 3–2 win against Austria, and on 12 November, he scored the equaliser against Wales in a 1–1 draw. He continued this scoring run in 2017, with goals against Georgia, Wales, and Moldova, putting him ahead of teammate Dušan Tadić as the group's top goalscorer.
With his partner Kristina, Mitrović has a son, named Luka. He is a lifelong supporter of both Partizan and Newcastle United.As of match played 26 August 2017
As of match played 5 September 2017
As of match played 2 September 2017
Serbian SuperLiga: 2012–13
Belgian Pro League: 2013–14
Belgian Super Cup: 2014
EFL Championship : 2016-17
UEFA Under-19 Championship: 2013
Serbian SuperLiga Team of the Season: 2012–13
UEFA Under-19 Championship Golden Player: 2013
UEFA Under-19 Championship Team of the tournament: 2013
Belgian Pro League Top scorer: 2014–15