David Taylor Price was born in Murfreesboro, Tennessee. He grew up as an Atlanta Braves fan and was a standout on the Blackman High School baseball and basketball teams.  In his high school career, he compiled a 0.43 earned run average (ERA) and 151 strikeouts. He received the Rutherford County MVP Pitcher (2003 and 2004), the Co-District 7AAA Pitcher of the Year with Michael Alcorn his senior season, and the Rutherford County Male Athlete of the Year in 2002, 2003 and 2004. He played in the 2004 High School All-America Game in Albuquerque, New Mexico.

Though Price was drafted in the 19th round by the Los Angeles Dodgers out of high school, he did not sign, and instead chose to attend Vanderbilt University on an academic scholarship. He pitched for the baseball team for three seasons.

In his freshman season in 2005, Price was honored as a Freshman All-American by both Baseball America and Collegiate Baseball. That year he went 2-4 with a 2.86 ERA in 19 games, compiling 92 strikeouts in 69 1/3innings pitched.

In 2006, he set a school single-season record in strikeouts with 155 while walking only 43 batters. In six starts early in the season, he recorded 10 or more strikeouts each game, including a 17-strikeout performance in a game against Arkansas. That year, he was one of five finalists for the Golden Spikes Award and a semifinalist for the Roger Clemens Award. He was also named to the third-team All-American by the National Collegiate Baseball Writers Association, first-team All-South Region by the American Baseball Coaches Association and second-team All-SEC by the coaches in that conference.

As a junior, he was the nation's top strikeout pitcher, striking out 194 batters over 133 1/3 innings, breaking his own school record. His last start against SEC competition came against Mississippi State in the SEC Baseball Tournament. Price pitched a complete game, going nine innings while giving up five hits, two runs, and striking out 11 batters with no walks. His last start at the college level came against Austin Peay in Vanderbilt's first game in the 2007 Nashville Regional. Against Austin Peay, Price retired 17 batters via the strikeout in nine innings of work while yielding just five hits, one run, and two walks. Price won several major national awards, including college baseball's top honor, the 2007 Dick Howser Trophy, and the 2007 Brooks Wallace Award. Price was the first player to have a clean sweep of all the college baseball awards.

In the summer of 2005, Price pitched for the United States National Team. He went 2-0 with a 1.26 ERA in five games, tallying 39 strikeouts and 13 walks over 28 2/3 innings. In the summer of 2006, he helped the United States take home the gold medal in the World University Baseball Championship held in Cuba. In eight starts for the United States, he was 5–1 with a 0.20 ERA.

Price signed his first professional contract on August 15, 2007. The six-year contract was worth $11.25 million, including a $5.6 million signing bonus. After the contract was approved by the MLB, he was added to the Devil Rays 40-man roster before being optioned to the minor leagues to begin his career.

Price was first assigned to pitch for the Vero Beach Devil Rays of the Class A-Advanced Florida State League. He started six games for Vero Beach, compiling a record of 4-0 and had an ERA of 1.82 with 37 strikeouts in 34 2/3 innings pitched.

He made his major league debut with the Tampa Bay Rays on September 14, 2008, against the Yankees. He was the winning pitcher in Game 2 of the 2008 ALCS against the Boston Red Sox, earning a post-season victory before winning a regular season game. He recorded the final four outs in Game 7 of the 2008 ALCS, earning his first career save and eliminating the defending champion Red Sox. He then pitched 2 1/3 innings in Game 2 of the 2008 World Series against the Philadelphia Phillies, giving up two earned runs but nevertheless earned his second postseason save.

On May 30, 2009, Price collected his first major league regular season win with a 5–2 victory over the Minnesota Twins in which he struck out 11 batters in under 6 innings. 

He finished the 2010 season tied for second in the American League, with Jon Lester, in wins (19) and in third place in ERA (2.72). Price finished 2011 with a 12–13 record, 218 strikeouts, and a 3.49 ERA in 34 games started.

In 2012, Price went 20–5 on the season (tying for the league lead in wins) with a league-leading 2.54 ERA. He pitched in the 2012 MLB All-Star Game. Price got his 20th win against the Chicago White Sox on September 30, making him the first 20-win pitcher in Rays franchise history, and he won the AL Cy Young Award after a tight race.

On July 31, 2014 Price was traded to the Detroit Tigers. With the Tigers, he went 4–4 over the final two months of the season, with a 3.59 ERA and 82 strikeouts

On July 30, 2015, Price was traded to the Toronto Blue Jays. He made 11 starts for the Blue Jays in 2015, and went 9-1, with a 2.30 ERA and 87 strikeouts. He finished the 2015 season with an 18–5 record and a 2.45 ERA, finishing second in Cy Young Award balloting 

Price signed a seven-year, $217 million contract with the Red Sox for 2106. He recorded a win in his debut with the Red Sox on April 5th. His first season was markedly different from the first to second half. In his first 18 starts, he compiled an 8–6 record with a 4.64 ERA and finished the season at 3.99 ERA with a 17–9 record. His 228 strikeouts also marked his second highest in his career, after his 2014 season split between Tampa and Detroit.

Price started the 2017 season on the 10-day disabled list with an elbow injury suffered in spring training. He was activated on May 29th and made his debut against the Chicago White Sox that afternoon.

On June 29th, Price was involved in a verbal altercation with Dennis Eckersley on the team's plane. Eckersley had criticized a poor performance by teammate Eduardo Rodriguez, prompting Price to yell, "Here he is, the greatest pitcher who ever lived! This game is easy for him!’’ at Eckersley, before doubling down with numerous repetitions of "Get the fuck out of here!" to the applause of several Red Sox players. He was criticized for his berating of Eckersley, as well as his refusal to apologize, by both the media and fans.

On July 28th, Price was again placed on the 10-day disabled list due to left elbow inflammation. He returned to the Red Sox on September 14th and was used from a reliever role for the rest of the season. In the 2017 American League Division Series against the Houston Astros, Price pitched ​6 2/3   2scoreless innings, including four innings in Game 3.

During spring training prior to the 2018 season, Price said he wished he had handled the situation with Eckersley differently and said he knew he could win the fans back by pitching well. He returned to the rotation to start the 2018 season and threw 14 scoreless innings in his first two starts, exiting the second one to a standing ovation from the crowd at Fenway Park. During the regular season, Price made 30 appearances (all starts) with a 16–7 record, 3.58 ERA, and 177 strikeouts in 176 innings.

In the postseason, Price started Game 2 of the Division Series against the Yankees. He allowed three runs on three hits and was removed after ​1 1/3   1/3innings, taking the loss. This was the tenth postseason game that Price had started during his career, all ten of which had resulted in losses for his teams.

His next postseason start was Game 2 of the Championship Series against the Houston Astros, which the Red Sox won, 7–5. He received a no decision as he did not complete the fifth inning. When Chris Sale became unavailable to start Game 5 of that series for health reasons, Price was called on to start again on only three days' rest, and earned the win, holding Houston scoreless through six innings while allowing just three hits and striking out nine. Winning 4–1, the Red Sox clinched their first trip to the World Series since 2013. It was Price's first win in 12 career postseason starts, and his third postseason win overall.

Price next started Game 2 of the World Series, holding the Dodgers to two runs on three hits and three walks in six innings while striking out five, and earning the win in a 4-2 Sox victory. He also pitched scoreless relief in Game 3 and warmed up in the bullpen for Game 4. He started Game 5 and  surrendered a home run to David Freese on his first pitch, but then retired 14 batters in a row. He was relieved in the eighth inning with the Sox leading, 5–1. Joe Kelly and Sale got the final six outs to clinch the World Series victory.

On October 31st, prior to the Red Sox victory parade, Price announced that he would not exercise an opt-out clause in his contract, saying that he wants to win in Boston. In early November, the New York City chapter of the Baseball Writers' Association of America (BBWAA) announced Price as the Babe Ruth Award recipient, honoring the MLB player with the best performance in the postseason. Later in November, Price was announced as the AL Comeback Player of the Year.

Price began the 2019 season as a member of the starting rotation, pitching to a 1-2 record with 3.75 ERA in six starts, until being placed on the injured list on May 6th, due to left elbow tendinitis. He was activated on May 20th, starting and getting the win in a game against Toronto. Price had a 7–4 record with 3.86 ERA in 20 starts, with 123 strikeouts in ​102 2/3   2/3innings. Price was placed on the injured list on August 8th, due to a left wrist triangular fibrocartilage (TFCC) cyst. He was activated from the injured list on September 1st and pitched that day, but then was held out of the rotation due to additional concern about his wrist. He did not pitch again during the season, finishing with 22 appearances (all starts), recording 128 strikeouts in ​107   1/3 innings and a 7–5 record with a 4.28 ERA.

On February 10, 2020, the Red Sox traded Price, Mookie Betts, and cash considerations to the Los Angeles Dodgers