Outfielders Ryan Abernathy and Zac Johnson provided the big swings to give the Mustangs that early breathing room.
Evan McDonald crossed the plate on an error in the third inning to open the scoring, then the long ball came into play.
With Lucas Powers on second, Abernathy sent the first pitch he saw over the wall for a two-run home run -- his first of the season.
Johnson connected for a solo homer in the next frame anchoring St. Joe to a 4-0 lead.
It's the club's first multi-home run game of the season.
Abernathy drove in another in the fifth for his third RBI of the game.
Mustangs' starting pitcher Trent Kinney did his part to keep the Diamond Spirit at bay.
Kinney held Omaha scoreless through seven innings, but ran into trouble in the eighth. The Diamond Spirit scored twice on two hits in the inning forcing manager Matt Johnson to give Kinney the hook.
Austin Aspegren came on in relief and struck out one batter to get out of the jam.
Jon Pomatto entered in the ninth with a chance to record a save, but could only get two outs while allowing two runs to score.
Brett Ash relieved Pomatto, and after surrendering a walk, struck out Creighton Wilke to end the game.
Kinney picked up his second win of the summer striking out five batters through 7 2/3 innings.
The Mustangs cap off a four-game road trip -- the team's longest of the season -- winning three contests. They return to Phil Welch Stadium Thursday night for a third consecutive game against Omaha.