In 2008, Musa was loaned to JUTH F.C. where he played 18 games, scoring four goals in his first two professional seasons for the Healers. He was subsequently loaned to Kano Pillars F.C., in the 2009–10 season where he set the league record scoring multiple crucial goals as Pillars finished second.

Musa was transferred to Dutch club VVV-Venlo in summer 2010, but the move was held up because he was only 17 years of age and therefore not eligible for an ITC in accordance with the current FIFA rules. He was officially eligible to play for VVV-Venlo on 14 October 2010 when he eventually turned 18 years of age.

In April 2010 under Coach Lars Lagerbäck, he was called up to join the Nigeria national football team camp prior to the 2010 FIFA World Cup in South Africa after helping the Nigerian team win in the 2010 WAFU Nations Cup where he scored a goal against Benin. In the same tournament against Burkina Faso, Musa’s goal deep into extra-time shot Nigeria into the finals of the tournament in Abeokuta. He was however forced out of the Super Eagles’ 30-man World Cup roster due to an ankle injury.

On 5 August 2010, at the age of 17, Musa made his debut for the Nigeria senior team in a qualification match for the 2012 Africa Cup of Nations against Madagascar, where he came on as a substitute for John Obi Mikel in a 2–0 win. Musa scored his first goal for the Super Eagles in a March 2011 friendly against Kenya.

Rated by Goal.com amongst the Hot 100 young football stars in the world to watch in 2011, Lolade Adewuyi of Goal.com put him on the list of Top Ten Nigerian International Players of 2010 and was also included in IFFHS list of the best 140 players in the world.

On 8 March 2011, Ahmed Musa won the AIT footballer of the year award (national). The ceremony was held at the Presidential Hotel, Port Harcourt, Rivers State. The event had in attendance, BBC African Footballer of the Year winner, Ghanaian Asamoah Gyan and the top officials from the Nigerian football federation including the president Aminu Maigari.

On 1 May 2011, Musa hit a brace to sink Feyenoord 3–2 and end any lingering fears of automatic relegation from the Eredivisie.

In August 2011, after returning from the 2011 FIFA U-20 World Cup in Colombia, Musa made his first appearance of the 2011–12 season at home against AFC Ajax and scored two goals.

In April 2011, Ahmed Musa was included in the Nigeria national under-20 football team squad to represent the nation in the 2011 African Youth Championship qualifiers, even though VVV Venlo had declared him unavailable for the tournament due to club commitments. After some intense negotiations with the Nigerian Federation, VVV Venlo and Musa’s representatives it was agreed that Musa will shuttle between the Netherlands and South Africa to participate in the tournament with the national team. After the opening game against defending champions Ghana, Musa won the most valuable player award and boarded the next flight back to the Netherlands.

In August 2011, Musa represented Nigeria U20 in the 2011 FIFA U-20 World Cup held in Colombia, where he scored three goals in five matches. Musa was included by FIFA in shortlist of 10 candidates for the Adidas Golden Ball, which was awarded to the most outstanding player of the FIFA U-20 World Cup.

On 7 December 2011, Ahmed Musa was one of the four nominees named for the Confederation of African Football Most Promising Talent Award, however the award went to Ivory Coast’s Souleymane Coulibaly.

On 7 January 2012, Musa signed for Russian side CSKA Moscow for an undisclosed fee.

On 17 September 2014 he scored an 82nd minute consolation goal in a 5–1 UEFA Champions League away rout to A.S. Roma. On 1 June 2015, Musa signed a new four-year contract with CSKA until the end of the 2018–19 season. He finished the 2015–16 Russian Premier League season as the 5th highest scorer, becoming one of only seven players aged 23 or younger to reach double figures for goals in each of the past two seasons in Europe’s top seven leagues.

On 8 July 2016, Musa moved to Leicester City for a club record £16.6 million. He scored his first goals with the club in a friendly against Barcelona in the 2016 International Champions Cup which ended in a 4–2 loss. He made his Premier League debut on 13 August 2016 in the club’s opening day 2–1 defeat to Hull City. He scored his first Premier League goal with the opener in a 3–1 victory over Crystal Palace on 22 October 2016.

By January 2017, Musa was yet to register an assist for the club, contributing an average of 0.5 key passes, 0.3 crosses and 1.2 successful dribbles per game.

In April 2017, Musa was involved in a dispute with his estranged wife Jamila, resulting in the police being called to his home. Shortly afterwards, the couple were divorced following “irreconcilable differences”.

On 30 January 2018, Musa returned to CSKA Moscow on loan for the remainder of the 2017–18 season.

On 4 August 2018, Musa moved to Saudi Arabian side Al-Nassr on a permanent deal. In October 2020, Al Nassr announced that Musa was leaving.

In May 2018 he was named in Nigeria’s preliminary 30-man squad for the 2018 FIFA World Cup in Russia. Though his performance against Iceland was superb, it was not even enough to keep the West Africans in the tournament as they were eliminated by Argentina On 22 June 2018, Musa scored twice in a 2–0 victory over Iceland in their second group match of the World Cup. In June 2019 he became the third most capped player for Nigeria’s national team, surpassing Nwankwo Kanu, after appearing in a friendly against Zimbabwe. He was named in the 2019 Africa Cup of Nations team by head coach Gernot Rohr.

On 24 January 2019, Musa confirmed the news of the death of his mother Sarah Musa on his Twitter page. She had previously been ill.