Second to Philadelphia's Allen Iverson with eight 40-point games last season, Pierce made 12-of-28 shots from the field and played just 28 minutes.
After averaging 29.6 points in three games against Cleveland last season, Walker was just 6-of-20 from the floor on Tuesday but made 7-of-8 free throws and added eight rebounds and seven assists.
The duo, who accounted for 51 percent of Boston's offense last season, combined for 37 points by halftime and 52 after three periods. Both players rested in the fourth after the Celtics built a 92-59 lead.
Lucas, who was 136-171 in four seasons with San Antonio and Philadelphia, saw his Cavs' debut spoiled early as Cleveland surrendered several easy baskets and never recovered.
Perimeter shooters Trajan Langdon and Wesley Person led the Cavaliers with 13 points apiece as they suffered their second straight home loss to the Celtics.
Cleveland outscored Boston, 30-16, in the fourth quarter to avoid the worst season-opening loss in team history.