Cano made his Primera División debut on 17 February 2008, starting in a 1–0 away loss against Huracán.[4] On 29 March, he scored his first professional goal by netting his team's only in a 3–1 loss at San Lorenzo,[5] and finished his first senior season with two goals in 11 appearances.
On 21 August 2009, Cano was loaned to newly promoted side Chacarita Juniors, for one year.[6] After featuring sparingly but suffering relegation he returned to Lanús, but after being rarely used by the latter, he was loaned out to Colón on 30 December 2010.[7]
On 26 July 2011, Cano moved abroad for the first time in his career, joining Categoría Primera A side Deportivo Pereira on loan until December.[8] The following 31 January, he moved to Paraguay's Nacional also in a temporary deal.[9]
In the 2014 campaign, Cano scored 27 goals and was the top goalscorer of the Clausura tournament; highlights included a hat-trick in a 4–1 away routing of Millonarios on 11 October.
Pachuca and loans
On 21 January 2015, Cano switched teams and countries again after agreeing to a contract with Liga MX side Pachuca.[11] He made his debut for the club on 1 February, starting in a 1–0 loss at Guadalajara, and scored his first goal on 4 March in a 1–1 CONCACAF Champions League away draw against Montreal Impact.
On 11 December 2015, after failing to feature in any league matches during the first half of the campaign due to a knee injury,[12] Cano was loaned to fellow league team León.[13] After being a regular starter, he returned to Pachuca and was mainly utilized as a substitute.
On 10 January 2018, Cano returned to Independiente Medellín on an initial six-month loan deal.[14] On 19 May, he extended his link until the end of the year,[15] and ended the season with 32 goals overall.
Vasco da Gama
On 27 December 2019, Germán Cano was announced as Cruzmaltino's first reinforcement for 2020.[16] In his second match for Vasco da Gama, Cano scored his first goal with the cruzmaltina shirt, in the last move of the victory over Boavista 1–0.[17]
On 6 December 2021, his departure from Vasco da Gama was announced.[18] In all, Cano played in 101 games and provided four assists and scored 43 goals. He is the club's second-highest foreign goalscorer in the 21st century and 2nd among foreigners.[19]
Fluminense
On 27 December, Cano signed with Fluminense, with a contract until 2023.[20]
On 26 May 2022, he scored his first hat-trick in the historic 10–1 away thrashing of Oriente Petrolero, a match valid for the last round of the Copa Sudamericana group stage.[21]
At the end of the 2022 season, Cano was the top scorer of the Campeonato Brasileiro Série A 2022 with 26 goals.[22] Also in the 2022 season with the tricolor shirt, Cano was the top scorer of the Copa do Brasil with 5 goals.[23] In all in the 2022 season he scored 44 goals.[24]
On 4 October 2023, he scored the winning goal in the 87th minute in a 2–1 away victory over Internacional in the second leg of Copa Libertadores semi-finals, having also scored a brace in a 2–2 draw in the first leg, which qualified his team to the final.[25] On 4 November, he scored the first goal for Fluminense in a 2–1 victory over Boca Juniors after extra time in the Copa Libertadores final.[26]