Put into bat in the day-night encounter at the Sardar Patel Stadium, Motera, Karnataka rode on a 162-run opening partnership between Agarwal (125) and Robin Uthappa (87) to post an imposing 359 for seven.
In reply, the Harbhajan Singh-led side was bundled for 203 in 38.2 overs.
With a cushion of runs at their disposal, Karnataka bowlers, led by medium-pacer Abhimanyu Mithun, made the strong Punjab batting look ordinary as Mandeep Singh top-scored with 76 runs.
The young Agarwal, who was declared the Man of the Match, made his presence felt in the domestic circuit by smashing 125 in 100 deliveries, the knock laced with 10 fours and 3 sixes.
Uthappa, at the other end, also made merry with a 81-ball 87, striking 9 fours and 3 sixes.
Not content with the opening onslaught, one-down Karun Nair soon took over from Uthappa, who fell to medium-pacer Baltej Singh, and struck a fluent 86 off 71 balls.
Nair stitched a second-wicket 85-run partnership with Agarwal and after the opener's departure managed a 87-run third-wicket stand with Manish Pandey (40).
Finally Baltej did get Nair out, but only when the damage had been done and the batsman had hit 8 fours and a sixes.
Punjab's pace spearhead Sandeep Sharma though did try to pull things back and was on hat-trick in the last over of the innings but the counter-attack came too late.
Sharma and Baltej shared three wickets apiece as the Karnataka bowlers bled runs aplenty.
On the batting front, Punjab, who had a mountain to climb, fought with a second-wicket 82-run partnership between Mandeep and Amitoze Singh (46) but the 350 plus score proved just too much to conquer.
Karnataka 359/7 in 50 overs (Mayank Agarwal 125, Robin Uthappa 87, Karun Nair 86; Sandeep Sharma 3-68, Baltej Singh 3-59)
Punjab 203 all out 38.2 overs (Mandeep Singh 76, Amitoze Singh 46; Abhimanyu Mithun 3-37, Stuart Binny 2-62).
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