Segura, who leads the National League with 129 hits, sent home Rickie Weeks with a first-inning single, igniting a three-run uprising, and made it 4-0 for Milwaukee with another RBI in the next inning.
The all-star shortstop came out of the contest in the sixth with tightness in his right forearm.
Tom Gorzelanny (2-4) collected the decision, yielding four runs on six hits over 5 1/3 innings, walking one and striking out four.
Jim Henderson picked up his 12th save after the game was delayed by rain for 1, hour, 45 minutes in the bottom of the ninth.
Collin McHugh (0-2), recalled from Class AAA Colorado Springs Friday, took the loss, allowing six runs on nine hits over five innings.
Wilin Rosario belted a three-run homer and Troy Tulowitzki went 3-for-4 with a solo shot and two RBI for the Rockies.