de los Santos began in the academy of Peñarol, prior to heading off to Almagro Baby Fútbol and Ferro Carril Salto of his hometown.[3] After a further youth stint in the ranks of River Plate, de los Santos' senior career began with Danubio in 2013.[1][4] He made his pro debut on 25 October in the Primera División, as he came off the bench with fourteen minutes left for Camilo Mayada.[1] In May 2014, de los Santos scored his first goal in a draw with Sud América as Danubio won the 2013–14 title.[1] A total of eighty-three appearances, ten of which arrived in continental competition, came in five years alongside three goals.[1]
On 30 June 2017, de los Santos agreed a loan to Millonarios of Colombia's Categoría Primera A.[5][6] Two goals came as they won the 2017 Clausura.[1] June 2018 saw Millonarios sign de los Santos permanently.[1] He would move clubs again one year later, though did manage to take his overall tally to eighty-three matches and six goals in the preceding months - winning the 2018 Superliga Colombiana in the process.[1] On 18 July 2019, de los Santos secured a one-year loan move to Argentina with Vélez Sarsfield; with a future purchase option.[7][8][9] He made seven total appearances, before returning to Millonarios in June 2020.[1]
However, de los Santos made a return to Vélez Sarsfield in February 2021, signing a deal until the end of 2023.[10] In 2023, he was loaned to Chilean side Colo-Colo.[11]