With the score tied 2-2, Alex Rios collected a leadoff single off Jeff Gray (5-1) and Pierzynski followed by belting an 0-2 pitch into the right-field bleachers.
The big hit handed the victory to Matt Thornton (3-6), who tossed a scoreless eighth. Addison Reed got his 17th save despite allowing two hits and a run in the bottom of the ninth.
Francisco Liriano, obtained by the White Sox from Minnesota in a Saturday trade, made his first start for Chicago against his former team, holding the Twins to two runs on four hits over six innings.
The win evened the three-game series and gave the American League Central-leading White Sox a 2 1/2-game advantage over second-place Detroit.
Denard Span went 4-for-5 with an RBI for Minnesota.