Playing for the school's baseball team, he had a 4–2 win–loss record and a 1.95 earned run average (ERA) with 74 strikeouts in 44 innings pitched in his senior year.

Projected as a third or fourth round pick in the 2010 Major League Baseball Draft, Nicolino expected to honor the commitment.

[2][3] Nicolino made his professional debut for the Vancouver Canadians of the Low–A Northwest League in 2011, posting a 5–1 win–loss record and a 1.03 ERA.

His teammates voted him as the Lugnuts' Most Valuable Player, and he was named to the Midwest League Postseason All-Star team.

[6][7] On November 19, 2012, the Blue Jays traded Nicolino, Adeiny Hechavarria, Henderson Álvarez, Yunel Escobar, Jeff Mathis, Anthony DeSclafani, and Jake Marisnick to the Miami Marlins in exchange for Mark Buehrle, Josh Johnson, José Reyes, John Buck, and Emilio Bonifacio.

[10] After pitching to a 5–2 record with a 2.23 ERA, and being named a FSL All-Star, he received a promotion to the Jacksonville Suns of the Double–A Southern League in July.

[11] Pitching for Jacksonville in 2014, Nicolino had a went 14–4 with a 2.85 ERA in 28 starts, and was named the Marlins' Minor League Pitcher of the Year.

[15] The Marlins called up Nicolino for his first major league start on June 20, 2015, taking the rotation spot of Tom Koehler.

[23] On February 6, 2019, Nicolino signed a minor league contract with the Minnesota Twins that included an invitation to spring training.

[24] He opened the season with the Triple–A Rochester Red Wings, posting a 5.12 ERA with 13 strikeouts in 4 games (3 starts).

[32] On June 24, 2023, Nicolino signed with the High Point Rockers of the Atlantic League of Professional Baseball.