Having previously trained with the first team in the 2010–11 season, along with his brother (who then left the club for Chelsea at the time), Lukaku was first included in a senior matchday squad on 1 December 2011, remaining an unused substitute in Anderlecht’s 2–1 win at AEK Athens in the group stage of the season’s UEFA Europa League. His debut came the following on 21 March 2012 against Zulte Waregem, which saw Anderlecht win 2–1; Lukaku later said after the match: “it was the best day of his life”. Then on 6 April when he started in a goalless Pro League game at Standard Liège; he totalled six appearances as his team won the league that season.

On 21 July 2013, he came on as an 87th-minute substitute for Matías Suárez as Anderlecht won the year’s Belgian Super Cup 1–0 against Genk at the Constant Vanden Stock Stadium. However, after appearing two matches at the start of the season, Jordan announced his desire to leave the club to get regular first team football.

Lukaku made his Oostende debut, where he came on as a substitute in the second half and played 45 minutes, in a 1–0 loss against Lokeren on 31 August 2013. Since making his Oostende debut, Lukaku established himself as a regular in the first team, even he was in the substitute and in a match against Genk on 23 November 2013, he set up one of the goals, in a 4–0 win. However, Lukaku’s last appearance for the club came on 25 January 2014 against Waasland-Beveren. Lukaku never made another appearance for the club again, as he suffered a pubalgia that kept him out of the season. Despite this, Lukaku went on to make fifteen appearance in all competitions.

With his contract expiring at Anderlecht at the end of the season, Lukaku joined Oostende on a permanent basis, signing a four-year contract. Lukaku’s first game after signing for the club on a permanent basis came on 1 August 2014, playing his former club, Anderlecht, in a 2–0 loss. Lukaku continued to be in a regular in the first team at Oostende despite being absence on two occasions, including his sending off against Gent on 25 January 2015. In his first permanent season at the club, Lukaku went on to make thirty appearances in all competitions.

In December 2014, Jordan Lukaku was charged with speeding and had his driving license revoked for fifteen days, as well as, being fined €600. The following month, his closest friend, Junior Malanda, was killed in a car crash. Three months later, he was charged with the same offence and was banned from driving for a year. He was given a final warning and told that if he did it again, he would be jailed. The following year, he was charged with the same offence for the third time and was banned from driving for fifteen months.

Following his impressive performance at Oostende, Lukaku was called by the senior team for the first team. On 10 October 2015, Lukaku made his senior debut for the national team in a 4–1 win in a Euro 2016 qualification match against Andorra; the victory qualified his team to the finals. In his next game on the following 29 March, he replaced Guillaume Gillet in the 59th minute of a friendly away to Portugal in Leiria, and sent in the cross that was headed in by his brother as consolation in a 2–1 loss.

In the 2015–16 season, Lukaku started the season well when he set up one of the goals, in a 3–1 win over Mechelen in the opening game of the season, followed up by scoring his first goal for the club, in a 2–1 win over Westerlo, which he was named Team of the Week. Lukaku continued to be in the first team until he was absence from late-2015, due to injuries. Lukaku then scored his second goal of the season on 31 January 2016, in a 3–3 draw against Mouscron. After returning from injury in early-May, Lukaku scored from his injury, in a 2–1 win over Genk on 14 May 2016. Lukaku finished his second season, making thirty-four appearances and scoring three times in all competitions.

With a hint from the club’s president, stating that Lukaku could leave the club in the summer, it was announced on 22 July 2016, he signed with Italian club Lazio for €4 million plus a reported €1 million in performance-related bonuses. Upon joining the club, Lukaku was given a number six shirt and was presented to the club several days later.

Lukaku made his Lazio debut, where he made his first start and played the whole game, in a 4–3 win over Atalanta in the opening game of the season. He continued to remain in the first team until he suffered an injury during an international break that kept him out for a month. It was not until on 27 November 2016 when he made his return from injury, coming on as a substitute in the second half, in a 1–0 win over Palermo.

In the 2017 Supercoppa Italiana, Lukaku came on as a late substitute in a 3–2 win over Juventus at the Stadio Olimpico. On 23 December that year, he scored his first goal for the club, finishing from a Ciro Immobile pass to open a 4–0 home win over Crotone.

In May 2018, he was named in Belgium’s preliminary squad for the 2018 World Cup in Russia. However, he did not make the final 23.

On 5 October 2020, Lazio confirmed that Lukaku had joined Belgian club Royal Antwerp F.C. on a one-year loan.