The top moment of his career, however, did not come until late 2006, as Internacional faced against Barcelona in the FIFA Club World Cup. Luiz Adriano came in as a late substitute and helped the squad as teammate Adriano Gabiru netted the winner in the 82nd minute. Luiz Adriano scored the defining goal for Internacional in their 2–1 win over Al-Ahly during the semifinals of the tournament.
Luiz Adriano was transferred from Internacional to Ukrainian side Shakhtar Donetsk on March 2, 2007, for a €3 million price. With Shakhtar he won the Ukrainian Premier League. He scored the opening goal of the 2009 UEFA Cup Final which his team Shakhtar Donetsk went on to win 2–1 after extra time. Following the UEFA Cup, he had provided his club with many goals, holding the image of a target man.
On 16 February 2011, he scored the winning goal against AS Roma in a 3–2 away victory during the first leg of the UEFA Champions League Round of 16 and after being victorious across the two legs.