On July 31, 2014, Prado was traded to the New York Yankees in exchange for catching prospect Peter O'Brien and a player to be named later. A few weeks after his acquisition, he hit a walk-off base hit into center field to give the Yankees a win over the Chicago White Sox.
On September 16, 2014, Prado underwent an emergency appendectomy, resulting on the Yankees putting him on the 60-Day Disabled List, ending his season. In 37 games with the Yankees, Prado batted .316 with 7 home runs and 16 RBI. Overall in 2014, combined with both teams, Prado played 143 total games batting .282 with 12 home runs, 26 doubles, and 58 RBI.
On December 19, 2014, the Yankees traded Prado and David Phelps to the Miami Marlins for Nathan Eovaldi, Garrett Jones, and Domingo Germán. Playing primarily at third base, Prado enjoyed successful campaigns in 2015 and 2016, batting .297 overall in 1,086 at bats, with a .350 on base percentage, and a .405 slugging percentage. In 2016 he led all MLB hitters (60 or more plate appearances) in batting average against left-handers, at .424. On September 27, 2016, the Marlins announced a three-year, $40 million contract extension that would keep Prado in Miami through 2019.