López made his official debut with Chacarita Juniors on 22 August 2009 in a loss against CA Tigre, amounting 24 games in 2009–10 Argentine Primera División.

In July 2010, López joined Arsenal de Sarandí on a free transfer, where he established himself as a centre back,[1] helping the team win the 2012 Clausura.

[2][3] His performances drew attention from European clubs such as Arsenal, A.C. Milan, Málaga CF,[4][5] and Benfica, in the latter side as a potential replacement for his fellow countryman Ezequiel Garay.

[6] On 10 July 2013, López signed with Portuguese club Benfica on a five-year deal and with a €35 million buy-out clause, being initially loaned for one year to La Liga side Getafe CF.

[7][8] In 2014–15, he was guaranteed a place in Benfica and made his debut on 5 October 2014 in a 4–0 home win over Arouca in Primeira Liga.