CHICAGO -- Andrew Cashner gave up two first-inning runs, but nothing after through a six-inning outing as the San Diego Padres beat the Chicago Cubs 5-2 on Sunday afternoon.

The right-handed ex-Cubs prospect improved to 1-2 as the Padres took two out of three in the Wrigley Field series.

Left fielder Will Venable's two-out single in the sixth scored right fielder Matt Kemp with a go-ahead run, breaking a 2-2 tie.

Cubs left-handed starter Jon Lester (0-2) suffered his first loss since a 3-0 Cubs Opening Night setback to the Cardinals.

The Cubs started fast with a pair of first inning runs.

Right fielder Jorge Soler drove in lead-off batter Dexter Fowler with a base hit to center for his ninth RBI of the season. Soler then came home on left fielder Chris Coghlan's single to right, the 500th hit of his seven-season career.

Padres manager Bud Black was ejected after leaving the dugout to argue balls and strikes.

Shortly after, third baseman Will Middlebrooks evened the score with third home run of the season with none out in the second. His drive off Lester to the empty left field bleachers brought home catcher Derek Norris to force a 2-2 tie.

Lester left the game with runners on first and second and one out in the sixth. Right-hander Brian Schlitter then surrendered a single to Venable that scored Kemp with the go-ahead run.

Schlitter struck out shortstop Clint Barnes to end the inning.

Lester gave up six hits, three earned runs and walked two while striking out three.

Cashner departed with a 3-2 lead after six innings. He allowed two runs on five hits, walked two and struck out five.

First baseman Yangervis Solarte made it 5-2 with a one-out homer to the right field corner off Cubs right-handed reliever Jason Motte. The homer, Solarte's first of the season, also brought home center fielder Wil Myers.

The Cubs had runners on first and second with two out in the ninth off Padres right-handed reliever Joaquin Benoit, who struck out Soler to end the game and earn his first save.

Middlebrooks and second baseman Jedd Gyorko each had two hits for the Padres.

Sunday's game started with hazy sunshine but quickly clouded over as forecasts called for potentially heavy rainfall later in the afternoon on a getaway day for both teams.

Rain held off until the bottom of the eighth inning but play continued.

NOTES: The Padres return play against NL West foes on Monday, opening a three-game series at Colorado. Seventeen of San Diego's first 20 games are against division opponents, with the Cubs series the lone exception. ... Padres RHP long reliever Odrisamer Despaigne (1-0, 0.77 ERA) gets the opening start against the Rockies. He's filling in for RHP Ian Kennedy, who's on the disabled list with a strained left hamstring. ... Kennedy makes a minor league rehab start in Arizona on Monday and is expected to be activated next week and step back in the starting rotation. ... LF Chris Coghlan's RBI single that scored RF Jorge Soler in the first inning was the 500th hit of his career. ... LHP Jon Lester's put out throw to 1B Anthony Rizzo in the second inning on SS Clint Barne's grounder came complete with Lester's glove. Rizzo dropped the glove but held onto the ball for an out. ... RHP Gonzalez Germen was called up from Triple-A Iowa on Sunday after four scoreless appearances, going 2-0 with five strikeouts. ... OF Matt Szczur was optioned to Triple-A Iowa after batting just .200 in eight games. ... RHP Jake Arrieta (1-1, 1.98 ERA) makes his 100th career start on Monday as the Cubs open a four-game series at Pittsburgh.