Amassing numerous awards as a standout pitcher, Ranaudo was selected by the Texas Rangers in the 11th round of the 2007 Major League Baseball draft upon graduation, but did not sign a contract.

[5] He had a standout year in 2009, third in NCAA strikeouts and was a critical player in the Tigers' College World Series victory.

[8] Ranaudo was selected 39th overall in the supplemental First Round of the 2010 Major League Baseball draft by the Boston Red Sox.

He was then promoted to the Advanced-A Salem Red Sox of the Carolina League, where he went 5–5 with a 4.33 ERA in 16 starts, including 67 strikeouts and a 1.35 WHIP in 81 innings.

His season ended early due to injuries, going 1–3 with a 6.69 earned run average over nine starts in just 37+2⁄3 innings of work.

At the end of July, he was leading the league in both WHIP (1.09) and batting average against (.204), while posting an 8–4 record and a 2.95 ERA in 19 starts, which included an 8.7 K/9 rate.

In that start he collected his first career strikeout, striking out Derek Jeter, who coincidentally was his boyhood sports hero.

On January 27, 2015, the Red Sox traded Ranaudo to the Texas Rangers in exchange for pitcher Robbie Ross Jr.[17] He was sent down to begin the season with Triple–A Round Rock Express on March 28, 2015.

Ranaudo was traded on May 12 to the Chicago White Sox for minor league right-handed pitcher Matt Ball.

Ranaudo started in the majors again for the White Sox on July 27 against the Chicago Cubs at Wrigley Field and got his first MLB hit with a fifth inning home run.