Chasing 145 to win after Karnataka chose to bat, Tamil Nadu completed the job in 19.2 overs at the MA Chidambaram Stadium.
Murugan Ashwin remained not out on a breezy 34 off 20 balls, while skipper Vikay Shankar contributed 30 off 26 deliveries.
Karthik struck four boundaries and a six before being run out, while Ashwin's knock was laced with three fours and two sixes.
Karnataka saw a glimmer of hope after Rajagopal Sathish's departure, which made it 86 for five in the 14th over, but Ashwin and Karthik ensured there was no setback thereafter, in the end guiding their team to a comfortable win.
Ravikumar Samarth finished as the top-scorer with 40 runs, while four batsmen got out after scoring 16 runs each.
Brief scores:
Karnataka: 144/9 in 20 overs (R Samarth 40)
Tamil Nadu: 145/6 in 19.2 overs (D Karthik 45).
In other South Zone matches, Hyderabad beat Goa by 51 runs, while Kerala beat Andhra by 21 runs.
Brief scores:
Hyderabad: 224/4 in 20 overs (Tanmay Agarwal 91)
Goa: 173/5 in 20 overs (S S Bandekar 53).
Kerala: 175/7 in 20 overs (Vishnu Vinod 63)
Disclaimer: No Business Standard Journalist was involved in creation of this content
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