Blackburn (8-8) yielded two hits to win for the first time since June 29, and failed to allow a run in a start for the first time since May 9 against Baltimore.
He retired 21 batters in succession from the second through the ninth and finished with a season-high six strikeouts. Brian Fuentes made his Twins debut a successful one, a four-pitch strikeout to notch his 24th save.
Delmon Young added two hits and Danny Valencia scored for the Twins, who have won three in a row and extended their lead over Chicago in the AL Central to four games. The White Sox and Yankees play later Saturday.
Doug Fister (4-10) was the hard-luck loser as he scattered six hits and one run over seven innings, fanning six with two walks.
Valencia singled to begin the Minnesota third, advanced on a J.J. Hardy double and scored when Span followed with a base hit.
Meanwhile, Blackburn mowed down the Mariners lineup. He issued a one-out walk in the second inning to Ryan Langerhans then didn't allow another baserunner until a two-out walk to Chone Figgins in the ninth.
That signaled Fuentes' entrance -- his first with the Twins since being acquired from the Angels on Friday -- against Branyan, striking him out swinging to end the game.
Minnesota has won six of nine meetings with Seattle this season...This was Blackburn's first road victory since May 16 at Yankee Stadium...Twins second baseman Orlando Hudson left the game in the second inning with a right ankle sprain...Minnesota DH Jim Thome left the game with back stiffness...It was Seattle's second shutout loss this week, after being blanked 10-0 by the Yankees on Sunday.