The holders wrapped up the Tamil Nadu first-innings in 62.4 overs, just 28 minutes after the tea session.
At stumps, Karnataka were struggling at 45 for four after 14 overs, trailing by 89 runs.
Tamil Nadu batsmen started the innings with a cautious approach and kept consuming balls.
Electing to field, Karnataka bowlers made the best use of the slightly green top wicket and made early inroads.
He struck again two overs later to get rid off Baba Aparajith (1) with an inswinging delivery, which sneaked through the young batsman's defences.
Dinesh Karthik scored 11 off 20 balls but was unlucky to be given caught behind as the ball had grazed his chest, further reducing the side to 34 for three.
Tamil Nadu kept losing wickets at regular intervals and the pressure kept mounting with the runs trickling in at a snail's pace.
Resuming at 60 for four, Tamil Nadu lost the rest of the side for just 74 runs.
Karnataka struck once again after lunch when Sreenath Aravind dismissed Ramaswamy Prasanna (6) to send half the side to the hut. Opener Abhinav Mukund, who provided some resistance with his 137-ball 35, too was sent back when Vinay Kumar castled him.
Things could have been much worse for Tamil Nadu had Manish Pandey not dropped Mukund at second slip in the second over of the innings.
Indrajith and Malolan Rangarajan did the repair job for the side and added 31 runs for the seventh wicket. Off-spinner Rangarajan (11) perished when he gloved a short-pitched ball from Abhimanyu Mithun to leave his side stumbling at 100 for seven.