After starting the first 58 games, Walker sat "because he's tired," manager Clint Hurdle said.
Giving Walker a day off was a painless decision, with versatile and hot-hitting Josh Harrison available to start in his place at second base. Jose Tabata, in turn, replaced Harrison in left field.
With the Pirates having an off-day Thursday, Walker will have two days to regroup before Friday's opener of a homestand and weekend series against Milwaukee at PNC Park.
"We're also mindful that he played the last two seasons hurt," added Hurdle, citing lower-back stiffness and then a strained right-oblique -- both injuries occurring past the midway point of those seasons.
"He's not made of Teflon. He's been on the field a lot. He's been hit [by pitches, 10 times], he plays second and gets knocked down and taken out on slides ... that's a lot of activity, all over the place."
Walker's season-opening consecutive games started streak was the longest by a Pirates player since Jason Bay answered the first 79 bells of 2007.
Walker leads National League second basemen with 11 homers, and his 34 RBIs are tops in the Majors at the position.
Tom Singer is a reporter for MLB.com and writes an MLBlog Change for a Nickel. He can also be found on Twitter @Tom_Singer.Stephen Pianovich is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.