Uthappa tore apart Punjab bowling attack as the hosts toiled hard to take wickets.
He also weaved important partnerships of 130 and 89 for the third and fourth wicket with Ganesh Satish (55) and Manish Pandey (49) respectively.
The right-handed batsman Uthappa whose knock of 149 came from 182 balls that included 16 hits to the fence and two sixes, was unlucky to get run out.
Earlier, in reply to Punjab's modest 243 in the first innings, Karnataka did not get off to a good start. They suffered an early blow when opener K B Pawan was adjudged caught behind off Manpreet Gony's bowling, a decision which looked doubtful.
K L Rahul, making his Ranji debut, also failed to impress as he was caught and bowled by Sidhu.With Karnataka struggling at 2-52, Satish and Uthappa steered the visitors out of trouble.
Then after the fall of Satish's wicket, Uthappa, who hit a boundary of Karan Goel to bring up his hundred, got valuable support from Pandey.Pandey played an useful knock before lobbing a catch to Punjab skipper Pankaj Dharmani of the bowling of N T S Sidhu (2-86), who proved expensive.
At the end of the day's play, Amit Verma (21) and skipper R Vinay Kumar (7) were at the crease.Yesterday, Karnataka pacers R Vinay Kumar and Sreenath Aravind helped their team bundle Punjab out for a mere 243.
While this is Karnataka's first match of the season, Punjab have already 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: 346 for 6 in 90 overs (Robin Uthappa 149, Ganesh Satish 55, Manish Pandey 49, N T S Sidhu 2-86).