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Johnson (7-7), winning his third straight after six consecutive losses, allowed two hits, struck out four and walked one in seven innings for his 291st victory in a swift, 2-hour, 18-minute game.
The 44-year-old left-hander, who entered the game with a 1.98 career ERA against Chicago, is the second pitcher to ever go at least 10-0 against the Cubs. The other was Sal Maglie, who was 10-0 in 19 starts against Chicago from 1954 to 1958.
Harden, in his second start for Chicago after a trade with Oakland, allowed one hit in seven innings — Alex Romero's first major league home run to lead off the sixth. It was the first run Harden allowed in 10 1-3 innings since joining the Cubs.
Harden (0-1) went seven innings, striking out 10 and walking two in the NL Central leader's fourth loss in five games.
Arizona made it 2-0 against reliever Bob Howry in the eighth when Stephen Drew tripled over the head of Mark DeRosa in right field, scoring Chris Snyder from first.
The Diamondbacks hadn't even had a hard out before Romero pulled Harden's 1-2 pitch, just clearing the right-field fence to make it 1-0.
The Cubs, on the other hand, had plenty of well-hit balls against Johnson, but they were caught either at the wall or by the wide-ranging Chris Young in the left- and right-center gaps.
Micah Owings relieved Johnson and pitched a scoreless eighth. Chad Qualls came on in the ninth to get his second save in eight tries.
It wasn't easy. Qualls walked Ryan Theriot, then first baseman Chad Tracy bobbled pinch-hitter Kosuke Fukudome's grounder. Reed Johnson grounded into a double play, then Aramis Ramirez bounced out to second to end it.
The shaky finish came one day after Arizona closer Brandon Lyon gave up five ninth-inning runs in a 6-5 loss to the Los Angeles Dodgers.
Harden retired the first 12 batters he faced, seven by strikeout, before walking Tracy on a 3-2 pitch to lead off the fifth. Tracy took second on a wild pitch, but was stranded there.
Chicago got the leadoff runners on base to no avail with singles by Jim Edmonds in the third and Reed Johnson in the fourth.
Notes: Romero is playing right field in place of injured Justin Upton. ... Cubs OF Alfonso Soriano will report to Triple-A Iowa in Tucson on Tuesday to continue rehabilitation from a broken finger. ... Chicago RHP Kerry Wood will treat the blister on his finger with ointment then attempt to throw on Wednesday, manager Lou Piniella said. ... The Cubs fell to 21-29 on the road. ... Drew has seven triples.
