Alcantara, 26, becomes the third Marlins pitcher to start three consecutive Opening Days, joining Josh Johnson and Josh Beckett.
A lack of run support contributed to Alcantara's 9-15 record last season, when he posted a 3.19 ERA over 33 starts. In five major league seasons, the right-handed Alcantara owns a 20-34 record with a 3.49 ERA in 86 appearances, 79 starts.
"I think he's still getting better and he has room to get better," Mattingly said. "The whole part of Sandy's game here, from his routines, his work in between starts, his bullpens, everything's become more precise. He has a lot of expectations for himself."