Quentin rebuilt the cushion in the seventh.
Activated this week after spending the first six weeks of the season on the disabled list because of a left knee bone contusion, Quentin batted for reliever Nick Vincent and followed Yasmani Grandal's two-out single with a drive off reliever Chris Martin that sailed into the left field bleachers for his first home run of the season.
Erlin, who entered hitless in 11 at-bats over his eight previous games, singled twice, including an RBI single in the third inning that capped three consecutive two-run innings by the Padres.
On the mound, Erlin allowed four runs on nine hits. He struck out two and walked none and benefited from a defense that turned five double plays, including four in the first five innings. Huston Street, also a former Rockie, got three outs for his 13th save in as many opportunities.
Lyles, who saw his ERA increase to 3.50 from 2.66, had control problems from the outset. He issued first-inning walks to Everth Cabrera and Smith before giving up a two-two-run double to Yonder Alonso.
Tulowitzki, who had three hits, answered in the bottom of the first with his NL-leading 12th homer of the season.
But Smith, who played for the Rockies from 2007-11, made it 4-1 San Diego in the second. One out after Chris Denorfia doubled, Smith drove a 1-1 offering from Lyles over the center field fence for his fourth home run of the season.
The Rockies pulled to 6-3 on Gonzalez's sacrifice fly in the fourth and Jordan Pacheco's RBI single in the fifth.
NOTES: San Diego right-handed reliever Donn Roach (1-0) will start Sunday's series finale against the Rockies in place of Andrew Cashner, who was placed on the 15-day disabled list because of soreness in his pitching (right) elbow. Roach be opposed by Colorado's Juan Nicasio (4-2). ... The Padres recalled RHP Kevin Quackenbush from Triple-A El Paso to fill Cashner's roster spot. ... Lyles' previous career high for walks was five against Boston on July 3, 2011, while with Houston.