It's the third loss in four games for the Padres (28-50), who sit at the bottom of the National League West. The fourth-place Rockies are three games ahead.
With Colorado leading 2-0, John Baker singled to right field to lead off the sixth against Rockies starter Jeff Francis (1-1), who had given up just two hits prior. Baker advanced to second on a sacrifice bunt, then watched as Francis walked Chris Denorfia on five pitches.
But Logan Forsythe, who entered the game hitting .286 with runners in scoring position, got under a fastball, popping it straight up to left field. Chase Headley then grounded into a force at third to end the inning.
Francis only struck out one batter, but he mixed speeds well -- topping out at 88 miles per hour and slowing down to the 60s.
"He's not like some of the other guys really below the hitting speed, like [Jamie] Moyer," Baker said. "But he pitches and that's the kind of effort you need in this ballpark, a guy who changes speeds. He kept his fastball at a different range so that guys are never on the same speed, and that's why it's difficult to wait."
The Rockies responded by shelling Marquis (1-4) for four runs -- three earned -- in the bottom of the frame by way of three consecutive extra-base hits. The first, a Carlos Gonzalez triple to right field, scored Dexter Fowler, then himself.
As Gonzalez slid face-first into third, Forsythe overthrew the bag from second base, sending the ball high into the seats. Gonzalez was then awarded the free trot home to make it 4-0.
Michael Cuddyer followed with a double and scored on a Tyler Colvin triple. Colvin scored the fourth run of the inning when San Diego shortstop Everth Cabrera misplayed a ground ball.
"Putting Dexter on was something I didn't want to do," Marquis said. "I wasn't able to put them away. Left a few balls up -- probably only the two mistakes I made all night."
The loss snapped a streak of four consecutive quality starts for Marquis, who pitched with the Rockies in 2009. Marquis hadn't allowed five earned runs in a game since May 15.
"The extra-base hits were his undoing," said San Diego manager Buddy Black. "They nicked him for some runs early, but 2-0 in the fifth in this park is anybody's game."
Marquis has been a tough-luck loser this season, as the Padres have scored eight combined runs in his last five starts.
"My job is to get guys out, try to execute as many pitches as possible and give my team the win," Marquis said. "I don't tend to worry about it as much. When you're younger, it tends to bother you more, but as you get older you learn that it is what it is. You can only control your job."
Compounded with the inability to put together rallies, Black said the Padres simply couldn't hit another "slow-throwing lefty," which has been a riddle all year.
"That has given us trouble," Black said. "We can't explain it, whether our guys are too aggressive, too jumpy, trying to do too much. We can't string at-bats against that type."
Said Francis, "I'm just commanding both my curveball and my changeup, throwing them both for strikes and being able to throw them for balls."
Francis was pulled after six innings -- his 82 pitches had exceeded the Rockies' 75-pitch limit for their four-man rotation -- and Carlos Quentin gave a rude welcome to the replacement, Tyler Chatwood, smacking his seventh home run of the season to lead off the seventh inning, making the score 6-1.
Will Venable plated another run in the eighth with a line drive to left field to make it 6-2, but the Padres again failed to take advantage of another scoring situation.
Headley and Quentin struck out swinging with runners on first and second for the first two outs, then Rockies reliever Rex Brothers got Yonder Alonso to fly out to right field to end the threat.
Left-handed reliever Alex Hinshaw then gave up four runs in the bottom half on a pair of two-run homers by Cuddyer and Wilin Rosario.