Tulowitzki homered leading off the second and had a run-scoring fielder's choice in the third. Todd Helton had an RBI double in the four-run third.
Buster Posey made his first start at first base and threw out a runner at home on a squeeze play. He drove in runs with a double in the first and a single in the fifth.
While the 2010 NL Rookie of the Year isn't expected to be there much during his return season from season-ending leg and ankle injuries sustained last May 25 in a collision at the plate with the Marlins' Scott Cousins.
"He feels great," manager Bruce Bochy said. "He's coming out of these games with no issues. That's good news for us. He's getting more and more comfortable in all facets of the game."
Juan Nicaso gave up 10 hits and three runs in 5 2/3 innings for Colorado and Travis Blackley gave up a run and four hits in two innings for the Giants.
San Francisco reliever Jeremy Affeldt yielded three hits and two runs for the loss.
Hector Sanchez homered, his fourth, and hit an RBI double for the Giants.
"He can hit, he always has," Bochy said of Sanchez. "He's got the ability from both sides and he doesn't really have a hole. He's a smart hitter. He knows what he wants to do up there. He's got a great gift."
The Giants other squad beat the Reds 6-4 in Goodyear.