The defending Western Conference champion Canucks rallied from a two-goal deficit to force the first overtime of the NHL season, but neither Mikael Samuelsson nor Alex Burrows could score in the shootout.
Pittsburgh began the campaign without star Sidney Crosby, who has yet to be cleared for contact by doctors after he missed the second half of last season with post-concussion symptoms.
Marc-Andre Fleury stopped 31 shots in regulation and overtime to get the win.
Roberto Luongo allowed the two shootout goals after making 22 saves.
After capturing the Western Conference title last season, the Canucks were swept by Boston in the Stanley Cup finals.