McCutchen unloaded a two-run shot in the first inning and added another in the seventh while Walker smacked a solo homer among five hits and scored four times in the rout.
Casey McGehee went 3-for-4 with a two-run single while Clint Barmes added two hits and an RBI as the National League Central-leading Pirates went into the All-Star Game break with their sixth win in seven contests.
A.J. Burnett (10-2) turned in his 12th straight start without loss, taming the Giants on two runs over 6 1/3 innings, surrendering four hits while walking two and fanning five.
San Francisco's Tim Lincecum (3-10) lasted only 3 1/3 innings, yielding six runs on seven hits.
Pablo Sandoval knocked a two-run homer as the Giants fell for the seventh time in nine games.