Although Deportivo Cali declined to take part in the first Liga Femenina Profesional tournament in 2017 alleging that they lacked the financial resources to field both a men's and a women's team,[1] the requirement issued by both CONMEBOL and DIMAYOR ahead of the 2019 season to field a women's team in order for the men's team to be allowed to compete in international competitions compelled Deportivo Cali to found their professional women's football section, as the men's side qualified for the 2019 Copa Sudamericana on sporting merit.

[5] This title allowed them to take part in the 2021 Copa Libertadores Femenina played in Paraguay, in which they had a perfect group stage with three wins in three games only to be defeated by Uruguayan side Nacional in the quarter-finals.

[8] The runner-up finish in the league qualified Deportivo Cali for the 2022 Copa Libertadores Femenina, in which they started their campaign with a 2–1 win over defending champions Corinthians.

Las Azucareras advanced out of the first stage of the tournament in fourth place with 26 points behind Atlético Nacional, América de Cali, and Santa Fe, after winning seven matches, drawing five, and losing the remaining two, and for the following stage of the competition they were drawn into Group B along with crosstown rivals América, Millonarios, and Llaneros, clinching qualification for the finals after winning the group with 12 points and a higher goal difference than Millonarios.

Just like in 2021, they faced Santa Fe in the final, however, this time Deportivo Cali won both matches in the series (2–1 at home and 2–0 in Bogotá with a brace by Manuela Paví) to claim the trophy.