With Ginobili missing due to a left hamstring injury, the Spurs (30-11) handed Memphis a third straight loss by a margin of at least 20 points.
"It was one of our better games," San Antonio coach Gregg Popovich told reporters. "(But) when something like (tonight) happens, it's because the other team is having a tough night."
Tim Duncan netted 19 points and eight rebounds while Tony Parker added 17 and 11 assists as San Antonio cruised after a slow start.
Memphis took a six-point lead after the first quarter but San Antonio took over from there as the home Spurs outscored their opponent 84-57 over the final three quarters.
Rudy Gay led the visitors with 17 points and eight rebounds after returning from a one-game absence due to a death in the family.
It was far from enough for the Grizzlies (24-13) who were hammered 99-73 by the Clippers on Monday and 104-83 by the Mavericks two days earlier.
"I'm at a loss for words right now," said Memphis coach Lionel Hollins. "When you shoot poorly it's a recurrent theme. When you turn the ball over it's a recurrent them and when you don't guard it's a recurrent theme."
All five Memphis starters scored in double figures but they got little help elsewhere.
The Spurs, on the other hand, were firing on all cylinders. They tallied 33 assists while shooting 58 percent from the floor. The victory was their 13th straight at home.
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