Farfán began his professional career with Alianza Lima of Peru, resigning in 2001. He made some appearances in 2001 on the first-team, and began to break through in 2002, and impacting Alianza with its 2003 Peru championship. In his final season with the club in 2004, Farfán scored 14 goals, helping the club to another Peru championship.

Farfán is an important player for the Peru national football team. Since making his debut for the side in February 2003, he has gained 95 caps and is second on the nation’s career goalscoring list with 27 goals.

Despite his talents, since late 2000s, he is also widely known for being indisciplined and controversial. He has involved in three major national football team scandals in 2007, 2010 and 2019; the two former caused him to be suspended from the national team.

Following that season he was purchased by Dutch club PSV Eindhoven after being scouted by Guus Hiddink, for a reported 2 million Euro transfer fee. Farfán made his debut in the Eredivisie on 14 August in a 5–2 win against RBC Roosendal. Almost two weeks later, Farfán’s European debut would come in the third qualifying round of the Champions League, a 5–0 win against Red Star Belgrade. PSV qualified for the final tournament and he played in all twelve games. In the group match against the Norwegian Rosenborg BK, he scored his inaugural European goal in 2–1 win. A month earlier, he had scored his first league goal, in a 4–0 win against SC Heerenveen. With PSV, Farfán won both the league and the cup tournament in his first season in the Netherlands. The Eredivisie would be won by PSV in the following three consecutive seasons. In the 2005/06 season, Farfán finished with 21 goals as club top scorer and fourth top scorer in the league. In his last season with PSV, Farfán was less dominant, partly due to an ankle injury he sustained during the 2007 Copa América. In March 2008, rumors began to circulate about a departure from Eindhoven.

On 5 June 2008, it was reported that PSV had reached an agreement with German side Schalke 04 over the transfer of Farfán for around €10 million. On 10 June 2008, the club officially confirmed the transfer of Farfán on a four-year contract. On 28 April 2012, Schalke announced that Farfán had signed a contract extension, which would keep him at S04 until 30 June 2016.

He was suspended for 18 months from representing the national football team of Peru. But on 3 July 2008, after an investigation and a review of the facts, the suspension was changed to three months (from the date of appeal in April 2008) and $10,000. Farfan scored the winning goal in the World Cup qualifier at home to Chile on 23 March 2013.

On 20 July 2015, after seven years at the club, Schalke confirmed that Farfán had joined Al Jazira Club for a reported fee of €6 million on a three-year deal, where he could earn up to €10 million a year.

Farfán left the club on 19 October 2016, because the club did not respect all the clauses in his contract.

On 28 January 2017, he signed with the Russian Premier League side FC Lokomotiv Moscow. The Russian team announced his signing after an irregular 2016, where he even was inactive for a hundred days after finishing in October 2016 a millionaire contract with Al Jazira. After 6 months of recovery, Farfán had a good season making goals that allowed his team to get the national title after 14 years.

In June 2018 he was named in Peru’s final 23-man squad for the 2018 FIFA World Cup in Russia. He started in their first group game against Denmark, which resulted in a 0–1 loss. Farfán started as a substitute in their second group game against France, coming on in the 46th minute to replace Yoshimar Yotún. His side were eliminated from the competition after another 0–1 loss. He missed their final group game against Australia as he was rushed to hospital after a suffering a concussion in training. Peru won their final game 2–0.

In Peru’s second game of the 2019 Copa América, Farfán scored a goal in Peru’s 3-1 victory over Bolivia. Farfán suffered an injury to his left knee prior to Peru’s last-eight clash against Uruguay, ruling him out of the rest of the tournament. The Peruvian Football Federation (FPF) confirmed the injury, with Farfán expected to be sidelined for 6 to 9 months. On 6 July 2019, Farfán underwent knee surgery in Barcelona, just hours before his team faced hosts Brazil in the 2019 Copa América Final. Peru went on to lose the game 3–1 in his absence.

He didn’t appear for Lokomotiv for 14 months from May 2019 due to knee injury and a following positive test for COVID-19. He made his first appearance upon recovery on 12 July 2020 in a game against FC Ufa and scored a late equalizer for his club in a 1–1 draw.

On 5 August 2020, Lokomotiv announced that Farfán left the club as his contract expired.