In April 2005, López signed for FC Porto for a transfer fee of €2.3 million, at the same time of compatriot Lucho González. His agents, Global Soccer Agencies (later renamed Rio Football Services), retained 50% of the player's rights– in the same transfer window, Luís Fabiano, whose rights were owned by GSA's sister company, "Global Soccer Investments" (75%), left. He scored seven Primeira Liga goals in his first season in 26 games, repeating the feat the following campaign while appearing in one match less; he also found the net in the 1–1 home draw against Rangers in the 2005–06 UEFA Champions League, adding two to help defeat Hamburger SV (also in that competition but in the following edition, 4–1 home win).
In 2005, López was called up to the Argentina national team by José Pékerman, and he made his debut against Mexico on 10 March in a 1–1 friendly draw. After fantastic Porto performances, he was summoned three years later by Alfio Basile for exhibition games with Egypt, Mexico, the United States and Belarus.