On the day, Punjab lost five wickets with an addition of only 11 runs on the board.
Karnataka's right-arm pacer Abhimanyu Mithun dealt crucial blows to Punjab middle-order, taking three scalps to reduce the hosts to 9-286 from 5-275 in their second innings in a space of less than seven overs.
Resuming at an overnight total of 173 for 2, with Yuvraj Singh (52) and Vishwas Bhalla (22) at the crease, Punjab suffered an early blow when the latter was adjudged LBW to R Vinay Kumar without any addition to his personal overnight score.
But India discard Yuvraj Singh continued to held on to his wicket and added 54 runs for the fourth wicket with Uday Kaul (43).Yuvraj's impressive knock 79 off 123 balls, which was studded with 13 boundaries, however was cut short by S Aravind, who took his first scalp of the day.
Skipper Pankaj Dharmani (51) continued to fight a lone battle but towards the end, the hosts lost the plot.
Chasing a small target of 140, Karnataka openers K B Pawan (65) and debutant K L Rahul (61) played sensibly to help the visitors achieve the target in 38.1 overs.
NTS Sidhu removed both the Karnataka openers, but not before they had taken their team close to the victory target.
Ganesh Satish (4) and Amit Khanna (1) later steered their team to a comfortable win, with Karnataka taking full five points.Mithun took three quick wickets. First, he had Kaul caught by substitute Stuart Binny (5-275) and then claimed the wickets of Karan Goel (0) and Harmeet Singh (6) by dismissing them in similar fashion.
Tailender Manpreet Gony (3) and Rajwinder Singh (0) also handed down catches, with Vinay Kumar bagging the two scalps.
Tottering at 9-286, Dharmani tried to put up some resistance, but lobbed a catch to C M Gautam giving Aravind another wicket. While this is Karnataka's first match of the season, Punjab had conceded the first-innings lead in their opening game against Uttar Pradesh that earned them just one point.
Brief scores:
Punjab 1st innings: 243 all out in 89.5 overs (Uday Kaul 94, Yuvraj Singh 39, R Vinay Kumar 5-61, Sreenath Aravind 4-63)
Karnataka 1st innings: 426 all out in 115.5 overs (Robin Uthappa 149, Ganesh Satish 53, NTS Sidhu 2-86)
Punjab 2nd innings: 322 all out in 96.3 overs (Yuvraj Singh 79, Pankaj Dharmani 51, Abhimanyu Mithun 4-94, Vinay Kumar 3-63, S Aravind 3-65)
Karnataka 2nd innings: 140 for 2 in 38.1 overs (K B Pawan 65, K L Rahul 61).