Dos Santos was a member of the Mexico under-17 team that won the 2005 FIFA U-17 World Championship held in Peru. He made his debut for the senior national team in a 1–0 victory over Panama on 9 September 2007, and represented "El Tri" at the 2010, 2014, and 2018 FIFA World Cups, along with the 2013 and 2017 FIFA Confederations Cup. With Mexico, Dos Santos has won the CONCACAF Gold Cup in 2009, 2011 and 2015, scoring in the 2009 and 2011 finals and winning the MVP award in 2009. He was also a member of Mexico's team that won the gold-medal at the 2012 Summer Olympics.