Chris Sale graduated from Lakeland Senior High School in Florida. After his senior year he was drafted in the 2007 Major League Baseball Draft by the Colorado Rockies, but chose not to sign and instead attended Florida Gulf Coast University.

In the summer of 2009, he pitched for the Yarmouth-Dennis Red Sox of the Cape Cod Baseball League and had a 1.47 ERAl. He was awarded the MVP in the Cape Cod All-Star Game.

During the 2010 season at FGCU, Chris was 11–0 with a 2.01 ERA in 103 innings with 146 strikeouts. He led the NCAA in strikeouts and was named the Atlantic Sun Conference "Pitcher of the Year" and the Collegiate Baseball "Player of the Year".

Chris was drafted by the White Sox in the 2010 MLB Draft and was assigned to the White Sox' Class A affiliate Winston-Salem Dash. He was then promoted to the White Sox triple-A affiliate Charlotte Knights and was called up to the majors in August. In his rookie year, he had a 1.93 ERA with 32 strikeouts.

In December 2016, the White Sox traded Chris to the Red Sox for Yoan Moncada, Michael Kopech, Luis Alexander Basabe, and Victor Diaz.

Chris finished either at or near the top of the American League in almost every significant pitching category in 2017. He led the league with 308 strikeouts, a 12.93 K/9 and had a 2.90 ERA.

The staggering strikeout total placed him behind only Pedro Martinez ‘ 313 strikeouts for the most by a Red Sox pitcher in a single season. He struck out double-digit batters 18 times that season, one short of Pedro’s franchise record.

For a while it seemed that Chris would cruise to his first Cy Young Award and was even garnering some MVP consideration, but by August he started to show signs of wearing down. He had some dominant outings that showed he was still the league’s best pitcher when he was on his game, but he was simply off a bit more as the season dragged on.

When Chris finally got his first taste of the postseason it didn’t go well. He was shelled for seven runs in Game #1 of the ALDS against the Astros. He pitched brilliantly out of the bullpen, nearly salvaging the series in Game #4, but John Farrell stuck with him a bit too long and it cost. Chris would end up being tagged with two of the Sox three losses in the series.

Chris maintained his role as one of the most dominant pitchers in baseball in 2018. For the majority of the year, he remained as effective as ever on the mound. During June, he had a 1.76 ERA over six starts, recorded 60 strikeouts in 41 innings and was named the AL "Pitcher of the Month". He was then named to the All-Star Game as the AL starting pitcher, for the third consecutive year.

At the end of July, he was placed on the disabled list due to left shoulder inflammation. He was activated on August 12th, and on August 18th, was again back on the 10-day disabled list again, due to inflammation of the same shoulder. He was finally re-activated in mid September and finished the year 12-4, with an impressive ERA of 2.11.

Chris was not at his most dominant in the post-season. He was effective against the Yankees, in Game #1 of the ALDS, allowing just the two runs over 5.1 innings, while striking out eight. In his ALCS and World Series starts, he only managed to pitch four full innings, giving up five runs in total.

He started Game #1 of the World Series and pitched 4-plus innings, giving up three runs on five hits and striking out seven in a no decision. He was more dominant is his relief appearances however, and his best moment of the postseason came in the clinching moments of the World Series, where he emphatically, struck out the side and got Manny Machado swinging for the final out of the World Series. That would be a memory that lives on with the Red Sox Nation for many years.

Shoulder inflammation knocked Chris out for most of 2019. He did have high points, like a 17K game vs the Rockies, but the Sox went 10-15 in his last 25 starts. He posted a 4.40 ERA, the worst of his career.

In February, 2020, the Sox announced that Chris would not be ready for Opening Day due to pneumonia. In March, it was announced that he would undergo Tommy John surgery, thereby ending his 2020 season.

In February, 2021, he was placed on the 60-day injured list as he continued to recover from Tommy John surgery. He was added to Sox active roster in mid-August, but his return was delayed by a rib cage injury at the start of 2022.

He returned in early July but suffered a fractured finger on his pitching hand in his second start back and then broke his right wrist in early August, during a bicycle accident.

In 2023, he had the most to prove but was back on the injured list in early June with a stress fracture of his shoulder blade. He finished the season strongly, allowing one or no runs in four of his final five starts.

In December, he was traded to the Atlanta Braves in exchange for Vaughn Grissom. His message to Red Sox nation was "Thank you, I'm sorry".