Blackley played for the Single-A San Bernardino Stampede in . He had a 5-9 record with a 3.49 ERA in 21 games, 20 of which were starts. He had 152 strikeouts in 121.1 innings, his strikeouts were second among all Mariners minor leaguers.
Blackley played for the Double-A San Antonio Missions in . His 2003 season was his most impressive of his minor league career. He led the Texas League with 17 wins; was second in ERA (2.61), fourth in strikeouts (144) and fourth in innings pitched (162.1). His 17 wins were the most by a Texas League pitcher since Jeff Reardon of the Jackson Mets in .
He participated in the Texas League Postseason All-Star game and was named to the World squad in the 2003 All-Star Futures Game at U.S. Cellular Field on July 15. Blackley was also named the Mariners minor league pitcher of the year by the organization.
In , Blackley was named by Baseball America as the #63 prospect out of 100 prospects. He was named the third best prospect in the Mariners system, behind pitchers Félix Hernández and Clint Nageotte, and was their top left-handed prospect. Blackley began the season in Triple-A with the Tacoma Rainiers. The Mariners, after trading Freddy Garcia to the Chicago White Sox, needed another starter and Blackley's contract was purchased on July 1, 2004. He made his major league debut on that same day against the Texas Rangers and allowed 4 runs on 6 hits in 5 2/3 innings and got the win. He became just the sixth pitcher in Mariners history to start and win on their major league debut.
After spending a month with the major league club in which he went 1-3 with a 10.04 ERA in 6 starts, Blackley was optioned back to Triple-A Tacoma on August 1, 2004. He had an 8-6 record with a 3.83 ERA in 19 games (18 starts) with Tacoma in 2004 before ending the season on the disabled list with shoulder tendinitis in his left arm.
Blackley missed the whole season while recovering from left shoulder surgery.
Blackley spent the majority of the 2006 season with Double-A San Antonio. After going 8-11 with a 4.06 ERA in 25 starts in Double-A, Blackley was promoted to Triple A Tacoma at the end of August. He made 2 starts in Tacoma and had a 1-1 record with a 4.09 ERA.
On April 1, , following the end of Spring Training, he was traded to the San Francisco Giants for outfielder Jason Ellison. Blackley was immediately optioned to Triple-A Fresno. Blackley played the whole minor league season with the Grizzlies. He went 10-8 with a 4.66 ERA in 28 starts. He was recalled on September 21, and on September 23 made his first major league start since July 31, 2004 against the Cincinnati Reds. Blackley won his debut, giving up two runs in the first inning and three hits in five innings. He walked four and struck out five.
Towards the end of the spring training, Blackley was placed on waivers. The Giants did not reclaim him and the Phillies outrighted him to Triple-A Lehigh Valley.