He graduated from Del City High School in Del City, Oklahoma. He attended Seminole State College. The 6-4, 227 pound right-hander was originally drafted by the Tampa Bay Devil Rays in the 34th round of the 2000 amateur entry draft. The Minnesota Twins then drafted him in the 29th round of the 2001 amateur entry draft. The Minnesota Twins signed him on May 21, 2002. From 2002 to 2007, he pitched 6 seasons for the Minnesota Twins minor league system. In 138 minor league appearances, he pitched 702 innings, posting 40-40 record with 434 strikeouts and a 3.68 ERA. His best season in the minors came in 2007, and after the season Baseball America ranked him as the Twins' No. 1 prospect.
Blackburn started his 2007 season with the Rochester Red Wings, where he pitched in 17 games. In those 17 games, he pitched 110.2 innings, posting a 7-3 record with 57 strikeouts and a 2.11 ERA. He was called up by the Twins in September. He made his major league debut on September 3, 2007, in a home game against the Cleveland Indians. In his major league debut, he pitched 1 inning of perfect baseball as a relief pitcher. He went on to pitch 6 games in 2007, all as a relief pitcher. He picked up his first hold on September 10, 2007, in a road win against the Kansas City Royals. Through his first 4 games as a Twins relief pitcher, he posted a 2.70 ERA; however, he gave up 8 earned runs in his last two appearances, raising his season total ERA to 7.71.
Blackburn pitched 9 innings in spring training for the Minnesota Twins, posting a 3.00 ERA, earning him a starting spot on the 2008 rotation. He picked up his first major league win on April 19, 2008, in a home game against the Cleveland Indians, pitching 7.2 innings of shutout baseball.
On May 1, 2008, Blackburn was hit in the face by a line drive off the bat of New York Yankees outfielder Bobby Abreu; however, he did not miss any time.
Through July 27, 2008, he had the lowest ERA for Minnesota Twins starting pitchers with a 3.69 ERA. He finished the season with an 11-11 record, an ERA of 4.05, and 96 strikeouts.
After the Twins and the Chicago White Sox ended the season with 88-74 records to top the AL Central, Blackburn started the 1-game tiebreaker to determine the division winner. Blackburn gave up just 4 hits, including a Jim Thome home run, but this home run proved to be the only scoring, as the Twins posted just two hits against starter John Danks.
Nick Blackburn was in the starting rotation for the entire season. His record was 11-11 and he had an ERA of 4.03 despite leading the AL in hits allowed (240). He also had 98 strikeouts and threw 3 complete games.
Blackburn started the 2010 season relatively strong, going 6-1 in April and May, with a 4.28 ERA. However, he struggled after that, going 1-6 with a 9.20 ERA over his next nine starts. On July 21, 2010, Blackburn was demoted to the bullpen and replaced in the rotation by Brian Duensing. In one relief appearance, Blackburn surrendered three earned runs in two innings. Through July 29, Blackburn was 7-7 with a 6.66 ERA.
On July 29, the Twins optioned Blackburn to triple-A Rochester to make room on the active roster for newly acquired closer Matt Capps. He was recalled on August 21, 2010, after Kevin Slowey was placed on the 15-day disabled list with a triceps injury.
On August 29, in his second start since being recalled, Blackburn retired 21 batters in a row. After walking Chone Figgins in the bottom of the ninth, he was relieved and Brian Fuentes struck out Russell Branyan.
Despite finishing the season with an ERA of 5.42, Blackburn finished with a record of 10-12 in 26 starts for the Twins.
Blackburn was in the starting rotation for much of 2011. He made several strong starts and pitched well until the end of July, when his pitching became much more erratic. Blackburn made his final 2011 appearance on August 21, leaving after 1.1 innings with a forearm injury. He finished the season with a 7-10 record and a 4.49 ERA. His control was an issue throughout the season, as he induced 54 walks in just 148.1 innings.
On August 20, after pitching to a 7.39 ERA for the season, the Twins outrighted Blackburn to Rochester.
Blackburn's 2012 season was an abysmal showing, finishing 4-9 in 19 starts. He also surrendered 143 hits in less than 100 innings.
On October 25, 2012, Blackburn had successful surgery to remove a bone chip in his throwing elbow, and is on track for spring training. In January, he was removed from the 40 man roster.
He did not pitch in the Majors in 2013, spending the whole season in the minors. Blackburn went on to appear in just 6 starts at the AAA level, recording an ERA over 5 before being shut down due to knee problems.
After being released by the Twins in late 2013, Blackburn encountered problems with his surgically repaired knee which he had surgery on in August. Because of a needed second surgery on his right knee, Blackburn spent the 2014 season recovering from knee surgery. Since his retirement, Blackburn went on to be a coach for his former high school, Washington High School in Washington, Oklahoma.
Blackburn’s repertoire consists of a 2-seam fastball, changeup, curveball, and slider. His 2-seam fastball is not overpowering, usually in the high 80’s to low 90’s; however, his 6-4 stand makes his fastball “appear to get on batters faster than the miles per hour would indicate.” He normally uses his 2-seam fastball to generate groundballs. He throws a nice curveball and tight slider. When pitching at his best, he can locate all four of his pitches for strikes, which can make him nearly unhittable.