Webb (1-1) allowed five runs and 12 baserunners, including four free passes.
"Walking four in seven -- with him that's not something you like to see," said manager Bob Melvin. "It wasn't a great outing and it wasn't horrific by any stretch, but I think with him, the standards are set a little bit higher after what he's accomplished."
Webb went to three-ball counts five times in the first three innings and was having some issues with his overall command.
"It wasn't his best location at times on his sinker," said Melvin. "You can always second guess. Maybe he should have thrown more breaking balls or worked inside more. He had some good changeups."
Webb actually complained about wet mound conditions in the second inning, calling out the grounds crew to put on some Diamond Dry.
"I felt like I slipped a couple of times in the first," said Webb. "I slipped once more the next inning, so I had them come out, but it was fine after that."
Eric Byrnes drove in all three D-backs runs in the losing effort.
The Rockies opened the scoring with two in the third on RBI singles by Todd Helton and Matt Holliday, as Webb allowed four consecutive batters to reach base.
The Diamondbacks answered back in the bottom of the inning on a two-out double by Stephen Drew and an RBI single from Byrnes.
Helton struck again in the fifth with another RBI single, driving in the 1,000th run of his career, but Byrnes tied the game at 3 with a two-run shot in the bottom of the sixth off Rockies starter Josh Fogg.
That set up a key sequence in the seventh: Kazuo Matsui had a leadoff single, and then John Mabry appeared to ground into a 3-6-3 double play, and though replays showed Conor Jackson stepped on the bag in time, Mabry was ruled safe.
"Obviously, that play had some ramifications," said Melvin. "But sometimes you have to deal with stuff like that, make your next pitch and get your next out -- but that wound up costing us."
Helton then lined to left for what would have been the third out, but instead Brad Hawpe stepped up and lined a two-run double down the right-field line to give Colorado the lead for good.
"That was a pretty good pitch," said Melvin. "He got it in there, and Hawpe just put a good swing on it and turned on one."
"I thought it was a pretty good four-seamer," said Webb.
"He threw me a 2-0 fastball in, and then he doubled up with it," said Hawpe. "He commands both sides of the plate pretty well, so after he threw me in the first pitch I felt I had to be ready for it. I can't let him come here again."
The Rockies wound up scoring all of their runs in the game after two men were out.
"It just seemed like I couldn't make the big pitch when I needed to," said Webb.
From there, the D-backs' offense, which has struggled in recent games, was completely shut down by a Rockies bullpen that retired all 12 men it faced, capped by Brian Fuentes working the ninth for his second save.
"We felt a little sluggish today, but we need to get after it tomorrow," said Melvin.