"Obviously I want to win," Samardzija said. "Being a starting pitcher, you have a big say as to how the game turns out. Obviously if my record isn't what I want it to be I need to do a better job."
Milwaukee jumped on Samardzija for two runs in each of the first two innings, taking advantage of several miscues by the Cubs on a soggy, cold day at Wrigley Field.
Segura singled with one out in the first, moved up on a wild pitch and scored on Jonathan Lucroy's base hit. Lucroy advanced when Lake mishandled his single to left and scored when Lyle Overbay reached on shortstop Starlin Castro's throwing error.
It was Castro's second error in three games and No. 7 in 40 games this season. The 24-year-old Castro had a career-low 22 errors in 159 games last season.
Segura added a two-run single in the second as Milwaukee opened a 4-0 lead. Welington Castillo had a costly passed ball that allowed the runners to move up to second and third before Segura hit a liner into center field.
Samardzija (0-4) allowed two earned runs and six hits in his shortest start of the season. His ERA increased from 1.45 to 1.62.
"He didn't have his best stuff today but he grinded out through five," Renteria said. "We had a couple plays that maybe extended his innings."
Barney connected in the second and Lake went deep in the third, but that was it for Chicago against Lohse (5-1). The veteran right-hander struck out two and walked one while improving to 6-6 in 21 career starts against the Cubs.
Will Smith tossed a perfect eighth for Milwaukee, and Francisco Rodriguez finished for his major league-best 17th save in 18 chances.