Maysonet, who was recalled from Class AAA Nashville last week to replace injured shortstop Alex Gonzalez, crushed a pitch from Cubs starter Chris Volstad into deep field with the bases loaded, capping a five-run sixth.
The infielder's only other homer came in 2009 as a member of the Houston Astros.
Jonathan Lucroy went 3-for-5 with an RBI for the Brewers, who clinched their three-game series against Chicago at Miller Park.
Shaun Marcum (2-1) tossed seven strong innings, handcuffing the Cubs on one run. The right-hander broke a streak of four straight no-decisions by yielding just three hits and a pair of walks while striking out six.
Volstad (0-5) remained winless in seven starts for Chicago, surrendering six runs on nine hits over six full frames.