DeSclafani was summoned from Double-A Jacksonville to make his major league debut in place of Fernandez, who has been advised to undergo Tommy John surgery to repair a torn ligament in his right elbow.
Miami's bats erupted for season-high totals in runs and hits (17), giving DeSclafani (1-0) plenty of breathing room. The 24-year-old right-hander allowed two runs on seven hits, walked one and struck out seven in six innings.
DeSclafani also registered his first big league hit and picked up two RBI.
Giancarlo Stanton extended his career-best hitting streak to 16 games, finishing 3-for-3 with a walk for the Marlins, who snapped a five-game skid.
It was a nightmarish outing for Paul Maholm (1-4). The Dodgers' left-hander surrendered 10 runs -- five earned -- on 11 hits and walked three in 3 2/3 innings.