Huntelaar played for PSV, De Graafschap, AGOVV Apeldoorn, Heerenveen, Ajax, Real Madrid and AC Milan,[3] before joining Schalke 04 in August 2010, for whom he was the top goalscorer in the 2011–12 Bundesliga with 29 league goals.

[7] He was scouted as a youth talent during this period by Go Ahead Eagles but the distance required to travel to the team's base in Deventer prevented him from joining the club.

He made his first team debut on 23 November 2002 in a 0–3 away win over Roosendaal, coming on as a second-half substitute for Mateja Kežman in the 76th minute.

[10] By the start of 2003, it was clear that Huntelaar's path into the first team was blocked,[11][12] therefore he was sent out on loan to his previous club De Graafschap, where his uncle was financial director.

[15] He then made his final appearance in the team on 29 May 2003 as De Graafschap lost 2–1 to FC Zwolle, confirming their demotion from the Eredivisie.

[17] At the start of the 2003–04 season, Huntelaar was again sent out on loan, this time to newly promoted Eerste Divisie side AGOVV Apeldoorn under coach Jurrie Koolhof.

[32] Huntelaar made his Ajax debut after the winter break and scored his first goal for the team on 5 February 2006 against former club Heerenveen in a KNVB Cup tie.

[33] In February, Huntelaar scored nine goals in seven matches for Ajax, including against Serie A club Inter Milan on his UEFA Champions League debut.

[38] In the KNVB Cup semi-final, Huntelaar scored a bicycle kick equalizer in injury-time against Roda JC, taking the game to extra-time.

Ajax went on to play in the UEFA Cup, where Huntelaar scored seven goals in seven matches, including against Werder Bremen, who would eliminate them in the third round.

[45] In the KNVB Cup, Huntelaar scored four goals in six matches, including an equalizer in the final against Alkmaar which ended in a 1–1 draw after extra-time.

However, Ajax were again knocked out of the Champions League at the qualifying stage, with Huntelaar missing a penalty in the first leg against Slavia Prague.

[49] Following the retirement of Jaap Stam in October 2007, Huntelaar was made temporary captain, pending the return of experienced midfielder Edgar Davids from injury.

[53][54] At the start of the 2008–09 season, Marco van Basten was appointed as Ajax coach and named Huntelaar permanent first team captain.

[55] Huntelaar scored nine goals in 15 appearances in all competitions before suffering torn ankle ligaments on 9 November 2008 in a league match against Sparta Rotterdam.

[57] At the start of December 2008, Real Madrid reached an agreement with Ajax to sign Huntelaar in the mid-season transfer window in January.

[61] Madrid had planned to add both Huntelaar and fellow new signing Lassana Diarra to their 2008–09 Champions League squad, but both players had already featured in the same season's UEFA Cup for previous clubs Ajax and Portsmouth, respectively.

[71][72] On 19 September, he scored his first goal for Schalke in a 1–3 home defeat against regional rivals Borussia Dortmund,[73] and he added two in a Champions League group stage match against Lyon on 24 November 2010.

[77] On 25 August, Huntelaar scored four goals, including two penalties, in a 6–1 win in the qualifying play-off round of the UEFA Europa League against HJK Helsinki, allowing Schalke to overturn a 2–0 first leg deficit and advance to the group stage 6–3 on aggregate.

After the resignation of head coach Ralf Rangnick on 22 September 2011,[78] former Royal Blues manager Huub Stevens returned to the team for their game against Hamburger SV on 2 October.

[79] Huntelaar powered his side to victory in Stevens' first game back, heading in a sensational opening goal and netting the winner in the 73rd minute with a flick past goalkeeper Jaroslav Drobný.

[83] Huntelaar scored a second-half brace in the club's 3–2 victory over Werder Bremen on the last day of the season, earning his side automatic qualification into the group stage of the Champions League.

[96] In 2019, he won with Ajax the Eredivisie, KNVB Cup and Johan Cruyff Shield; in addition, he played in the 2018–19 UEFA Champions League, in which his team reached the semi-finals.

[99] With his goal in the 1–2 defeat against Bayer Leverkusen on 3 April 2021, he became Schalke's oldest Bundesliga goalscorer at the age of 37 years and 234 days.

Huntelaar became top scorer in the tournament with four goals[101] including two in the final on 4 June 2006 to help the Netherlands beat Ukraine 3–0[102] and claim their first ever title at under-21 level.

[106] Due to the suspension of striker Ruud van Nistelrooy, Huntelaar was in the starting line-up against Slovenia and went on to score his first competitive international goal in the Netherlands 2–0 victory.

[107] Huntelaar was included in the Netherlands Euro 2008 squad, and scored in his only appearance in the tournament with the opening goal of their final Group C match against Romania in a 2–0 victory.

[118] He was the top goalscorer in the UEFA Euro 2012 qualifying competition with 12 goals, leaving him one shy of Northern Ireland's David Healy's all-time qualification record.

[125] Following the departure of Hamstra and Schreuder, Huntelaar took over the role of Technical Manager, reporting to the Director of Football, Sven Mislintat.