Fernando Salas was born and raised in Huatabampo, Mexico. Growing up he never thought about playing in the American Major Leagues, instead being an avid fan of Mexican League baseball. Said Salas: "There is a lot of money to stay in Mexican League. A lot of players in Mexican League have a chance, (at American baseball) but they want a lot of money." Although he watched little if any American baseball—the only game he can remember watching is the 1993 World Series between the Toronto Blue Jays and Philadelphia Phillies—he had a dream of proving he was good enough to play in the major leagues.

Salas first pitched professionally at age 20 when he was signed by the Saltillo Saraperos of the Mexican League. There his pitching coach was Sid Monge a veteran of ten years in American Major League baseball as a player and a coach in the St. Louis Cardinals minor league system. According to Salas, Monge was the reason he is now playing in the major leagues: "He pushed me. He said 'You can go to America'. He believed in me." Representatives from other major league teams took interest in Salas as well, with scouts from the Chicago Cubs, Kansas City Royals, Detroit Tigers and the Cardinals watching Salas pitch in the 2006 Mexican League playoffs.

The Cardinals were impressed enough to buy Salas' contract from Saltillo in February 2007. He reported for Spring training in Jupiter, Florida, remaining there for the entire season with the Cardinals High-A ball affiliate Palm Beach Cardinals. He advanced through the minor league system, playing for the Double-A Springfield Cardinals in 2008 and Triple-A Memphis Redbirds for the 2009 season. Salas began 2010 in Memphis but was called up to the majors for the first time on May 27, 2010. He made his major league debut the next day, pitching one scoreless inning. In 2011, he replaced Ryan Franklin as the Cardinals' closer, earning 24 saves in 68 appearances with a 2.28 ERA. Salas began the 2012 season with St. Louis, but after going 0-3 with a 6.32 ERA in 18 games, he was optioned to Triple-A Memphis. It was later learned that Salas had been hampered by a kidney stone, and once that medical situation passed he returned to St. Louis later in the season. He finished the 2012 season with a record of 1-4, 60 strikeouts, and a 4.30 ERA.

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