He appeared previously for Feyenoord Academy, Espérance de Tunis, and Columbus Crew and spent time on loan at Asante Kotoko.

After four years of professional football, Afful left Ghana for the first time to join Espérance de Tunis of the Tunisian Ligue Professionnelle 1.

In the summer of 2015, Afful moved to the United States and signed for Columbus, helping the club reach MLS Cup 2015 in his first season.

At the international level, Afful made his Ghanaian debut at the 2008 Africa Cup of Nations, helping Ghana to a third-place finish at that tournament.

[16] Afful scored his first two goals for the club in a three-match span in the spring of 2010, tallying against CA Bizertin on 28 April and ES Hammam-Sousse on 15 May.

He appeared 17 times without a goal as the Blood and Gold claimed their third consecutive league title, but did start in the Tunisian Cup final as Tunis defeated Étoile du Sahel.

[20] He went on to appear in every game of the tournament from the group stage on, helping lead EST to the 2010 CAF Champions League Final against TP Mazembe.

In the 22nd minute, he placed a left-footed, curling shot into the upper corner, a goal that gave Tunis a 1–0 victory and the second Champions League title in club history.

[33] Afful again played a vital role for EST in the Champions League, helping the Blood and Gold advance to their third consecutive final to take on Al Ahly.

[38] Afful then tallied the game-winning goal against Sfaxien on 2 April, helping Tunis claim their fourth league title in his five seasons at the club.

[18][39] He added ten more appearances in the 2013 CAF Champions League, but EST were defeated by Orlando Pirates in the semifinals and denied a fourth consecutive trip to the final.

[40] Afful then began the 2014 CAF Champions League by scoring in both the first and second qualifying rounds, helping Tunis advance over Gor Mahia and Real Bamako, respectively.

FIFA ordered Espérance to pay the remaining monies within one month of the ruling date; if they failed to do so, they would be docked six points in league play.

[50] After his contract with Tunis expired at the end of June, Afful joined Major League Soccer (MLS) club Columbus Crew SC as a Discovery Signing.

[51] He was recommended to the club by ex-Ghanaian international Joe Addo, who had played alongside Crew head coach Gregg Berhalter in the 1990s.

[52] Although the transfer was announced on 30 July 2015, Afful was only added to the roster after securing his visa and thus had to wait to make his club debut until 19 August.

[53] Afful missed several matches while on international duty but returned to start every game in Crew SC's run to MLS Cup 2015.

[56] Afful was rumored to be leaving Columbus ahead of the 2016 season, with reports from his native Ghana claiming that he would be joining Mersin İdman Yurdu when his contract expired at the end of 2015.

[62] Afful's 2017 season was marred by injuries: a knee laceration in March,[63] a sliced nerve in his hand in April,[64] a thigh strain in late summer,[65] and a sprained foot in October.

In the first leg of the conference semifinals against New York City FC, Afful scored three minutes into stoppage time to give Columbus a 4–1 victory; that goal would end up being the difference as the club advanced by a 4–3 aggregate scoreline.

In a home match against Atlanta United FC on 30 March, he collided with countryman Jonathan Mensah and suffered a fractured jaw.

[71] Afful missed eleven matches due to the injury, returning on 11 June and making his U.S. Open Cup debut in a victory over Pittsburgh Riverhounds SC.

[62] He missed the opening match of the season, a CONCACAF Champions League fixture against Real Estelí, after what was reported to be a stint in COVID-19 protocol, but returned to play against the same team a week later.

[82] Afful was a fixture in the lineup into the fall, providing two assists but also seeing a red card in a Hell is Real Derby draw with FC Cincinnati in July.

[96] Afful was recalled to the Black Stars in June 2012, as James Kwesi Appiah brought him in for 2014 FIFA World Cup qualifiers against Lesotho and Zambia.

[96] After appearing just twice in qualifying for the tournament, Afful was called up to the Ghanaian squad for the 2013 Africa Cup of Nations, alongside his club teammate Emmanuel Clottey.

[100] Afful appeared twice as Ghana were eliminated in the group stage, providing an assist in a draw against eventual world champions Germany on 21 June.

[101] After appearing in all six matches in Ghana's 2015 Africa Cup of Nations qualification run, Afful was named to the squad for the final tournament on 7 January 2015.

Afful scored his attempt in the penalty shootout as the eighth taker, but Ghana were defeated 9–8 on spot kicks; for the second time, he finished as an AFCON runner-up.

[105] Afful played every minute in the tournament, helping the Black Stars to a fourth-place finish after falling to Burkina Faso in the third place match.