Centre Luke James and full-back Joe Carpenter scored first-half tries before a penalty try and Jonny Hill's score gave Alex Sanderson's men a five-point haul and left the Chiefs with eight straight Premiership defeats this season.
It was also Exeter's 10th straight reverse in major competitions following their back-to-back setbacks against the Sharks and Toulouse in the European Champions Cup.
Rob Baxter's visitors, who also lost England winger Immanuel FeyiWaboso to a shoulder injury during the first half, fought hard in difficult conditions but Sale were worthy winners.
The hosts had picked up maximum points against Racing 92 last weekend and they remain unbeaten in the north west in all competitions so far this campaign.
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'Obsessed' Guardiola can't find solution to puzzle
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