[12] On 10 August 2005, he made his Sporting CP debut, coming on as a substitute for Custódio in the 73rd minute in a 1–0 home defeat to Udinese in their third-round qualifier in the UEFA Champions League.

[12][13] Nani made his Portuguese Liga debut on 28 August,[12] replacing Deivid in the 76th minute of a 1–2 victory over Marítimo at the Estádio dos Barreiros.

[19] He passed his medical on 6 June 2007,[20] and signed a five-year contract one month later, joining Portuguese compatriot Cristiano Ronaldo, with whom he lived at the start of his Manchester United career.

[26] Nani's Premier League debut came in United's opening match at home to Reading on 12 August as a substitute for Wayne Rooney, who had suffered a foot injury.

[31] On 16 February 2008, Nani put in a man of the match performance against Arsenal in the FA Cup Fourth Round, his goal and two assists helping United to a 4–0 win over their rivals.

[35] On 21 May, Nani came on as a substitute for Wayne Rooney in the 2008 UEFA Champions League Final as United defeated Chelsea 6–5 on penalties following a 1–1 draw after extra time.

[39] After Cristiano Ronaldo's transfer to Real Madrid in the 2009 close season, the weight of expectation was on Nani to step up from bit part player and replace his compatriot.

[62] Six days later, in a 3–0 home victory over West Ham United, Nani scored his first goal of the season and assisted Dimitar Berbatov in a Man of the Match display.

[67] He scored into an empty net after Tottenham goalkeeper Heurelho Gomes rolled the ball out to take a free-kick he thought had been given for handball; however, play was allowed to go on as referee Mark Clattenburg did not blow his whistle.

[74] It was thought Nani would miss up to three weeks as a result of this tackle and would return in April,[75] but he recovered in time to play 61 minutes of a 2–1 victory over Marseille on 15 March.

[76] Nani was revealed as a contender for the Professional Footballers' Association (PFA) Young Player of the Year award alongside teammate Javier Hernández on 8 April.

[82] Nani began the new season by putting in a man of the match performance and scoring twice against derby rivals Manchester City in the 2011 Community Shield, including a 94th-minute winner, as United came from two goals down to win 3–2 on 7 August 2011.

He played a neat one-two with Darren Fletcher before making his way through Stoke's defence and firing a low shot inside the left post.

With Manchester United leading 1—0, Nani was sent off in the 56th minute for a high boot on Álvaro Arbeloa; Real Madrid took advantage of their numerical superiority and scored twice to win the match 2–1, and the tie 3–2 on aggregate.

[96] Nani scored in Sporting's penalty shootout victory over Braga in the 2015 Taça de Portugal final, which earned the club their first trophy since 2008.

[99] He and his former United teammate Robin van Persie debuted 22 days later in a goalless home draw against Shakhtar Donetsk in the third qualifying round of the season's Champions League, with Nani starting.

[106] In his one season at the Mestalla, he suffered four muscular injuries over the course of the campaign – a contrast to his previous year in Turkey, where he played 64 games for club and country.

[113] He made his club debut on 2 March, coming on as a 70th minute substitute in Orlando's season opener at home against New York City FC; the game ended in a 2–2 draw, with Nani registering an assist on Dom Dwyer's equaliser.

[120][121] On 21 May, the MLS Disciplinary Committee suspended Nani for two games for making physical contact with referee Alex Chilowicz during a match at D.C. United five days earlier on 16 May.

[127] On 6 January 2023, during an A-League Men game against Brisbane Roar, he ruptured his anterior cruciate ligament in an accidental clash with opponent Connor Chapman, and was ruled out for the rest of the season.

[131] On 13 July 2023, Süper Lig club Adana Demirspor announced the signing of Nani on a one-year contract, with an option for a further year.

[141] Nani made his first appearance for the senior Portuguese team on 1 September 2006, and marked his debut with a goal in Portugal's 4–2 friendly defeat to Denmark.

[145] Nani received a call-up to Luiz Felipe Scolari's 23-man squad for Euro 2008 alongside Manchester United teammate Cristiano Ronaldo.

[146] During the campaign, Nani played three matches and started just one,[138] but did provide the assist for Hélder Postiga's goal during a substitute appearance in the 3–2 quarter-final defeat to Germany on 19 June.

[147] Nani's fourth international goal came in Portugal's final friendly match before their World Cup qualifying campaign started, a 5–0 victory over the Faroe Islands on 20 August 2008.

[160] Nani scored Portugal's first goal in the last match of the group stage, a 3–3 draw against Hungary on 22 June, to help the team qualify for the knockout round.

[162] During their quarter-final match on 30 June against Poland, Nani set up Renato Sanches' goal in regulation time and later scored Portugal's fourth penalty in an eventual 5–3 shoot-out victory, following a 1–1 draw after extra-time.

[164] In the final against host-nation France on 10 July, Nani was awarded the captain's armband after Cristiano Ronaldo was forced off in the opening 25 minutes of the match following a challenge from Dimitri Payet.

While being able to play on both wings, Nani was more comfortable on the right side, where he was known to utilise his pace along with intricate dribbling skills and trickery to create space in wide areas and provide crosses for teammates.

[170][171] Nani celebrated goals with a somersault referred to in Portuguese as a "mortal" ("leap of death"), similar to that of Obafemi Martins and Lomana LuaLua.