Buehrle, who will make his ninth opening day start for the White Sox on Friday in Cleveland, gave up a double to Erick Almonte in the second and Jeremy Reed's leadoff single in the fourth.
The left-hander struck out seven, two more than he had in his first four outings combined.
Brewers starter Marco Estrada, in the running to make a spot start depending on Zack Greinke's recovery from a broken rib, allowed two runs and seven hits in six innings. He struck out four and walked one.
Almonte had two hits for the Brewers, raising his spring average to .451. He will make Milwaukee's 25-man roster as a reserve outfielder.