Trailing by a run, Mike Fontenot hit a leadoff single against Arizona closer Jose Valverde, who entered the day as the Major League saves leader with 39.
Daryle Ward then followed with a pinch-hit single to put runners on first and second, before exiting for pinch-runner Felix Pie.
That brought Jason Kendall to the plate. Manager Lou Piniella's original plan was to have Kendall lay the bunt down, but he fouled two of them off before running the count full.
"There was one pitch that was good [to bunt], but the other one was a little high," Kendall said.
With the full count, Piniella elected to put the runners in motion on the next two pitches, but Kendall fouled off Valverde's offerings each time.
"He handles the bat as well as anyone we've got," said Piniella. "We had some speed on the bases, so we took a chance."
Piniella sent the runners a third straight time, but on this pitch Kendall swung and missed at what looked like ball four, and Fontenot was gunned down at third. Two out.
"The bottom line is I should have got the bunt down," Kendall said. "I didn't do my job."
Ryan Theriot drew a walk, and Jacque Jones hit a hard grounder to the right side that D-backs first baseman Tony Clark had to dive to reach before tossing to first for the final out.
"We've got to start scoring some more runs. That's really the bottom line," Piniella said. "We can't expect our pitchers to go out and give up one or two every time."
It was a little more disappointing loss because the Cubs jumped out for three runs in the first inning. They got help right out of the gate with a couple of unusual errors. Theriot drew a leadoff walk and took second on a missed catch by Arizona first baseman Conor Jackson on a pickoff throw.
Jones hit an infield single up the middle to shortstop Stephen Drew, who wheeled and tried to fire to third base, only to have the ball wind up in the stands on a bounce to score a run. Aramis Ramirez hit an RBI groundout, and Cliff Floyd followed with his fifth homer of the season to give the Cubs an early three-run lead.
However, Cubs starter Jason Marquis (10-8), had problems with D-backs center fielder Chris Young, as Young got one of those runs back with a leadoff homer in the bottom of the first, and the rest of them back with a three-run homer the next inning, part of a four-run second for Arizona. Young leads Major League rookies in homers with 28.
"Obviously, I didn't do my job protecting the lead," said Marquis, who allowed five runs in 5 1/3 innings. "I felt fine, but I left a few balls up in the zone. I missed my spot on both [Young homers]. I just didn't make pitches when I needed to."
Derrek Lee hit an inside-the-park homer in the third to cut the lead to a run. It was the first inside-the-park homer by a Cubs player since Sammy Sosa in 2001, and the second of Lee's career, the other coming with Florida in 2003.
Unfortunately, that's where the score would stay for the remainder of the game, as the D-backs bullpen hurled five shutout innings with Edgar Gonzalez (6-2) working two of them to earn the win.
"It seems like every time we do that [score early], we don't score for the rest of the game," Floyd said. "It was unfortunate because after Young's adventurous day, Marquis gave us a chance to win. We just have to find a way."
The Cubs return home for an important stretch as they battle for a division crown, starting with the second-place Brewers on Tuesday night.
"We have 10 games at home. We need a good homestand," said Piniella. "It's our last big homestand of the year, so we have to take advantage of it."