Harden fired in 28 points and added five assists for Houston, which broke a two-game losing skid.
Defino, meanwhile, returned from a two-game absence due to illness and pumped in 22 points to go along with eight helpers.
The Hawks couldn't preserve their four-game winning streak despite 21 points from Lou Williams.
Al Horford contributed a double-double of 18 points and 13 rebounds for Atlanta.
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