Ravikumar Samarth (81), Karun Nair (80) and Manish Pandey (73 not out) guided Ranji Trophy champions to 341 for six after resuming the day at 39 for no loss at the Chinnaswamy Stadium.
Rest of India had put Karnataka under pressure by dismissing them for 224 on day one but the hosts have managed to come out of the woods with a solid batting display.
Pandey's unbeaten 52-run partnership with captain Vinay Kumar (28 not out) towards the close of play further frustrated Rest of India. Both Pandey and Vinay had luck on their side as they were dropped on 50 and 6 respectively.
Change in position did not work for Uthappa as he chopped one on to his stumps off pacer Varun Aaron. He had made 10 in the first innings at the top of the order.
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Nair and Pandey stitched an important 106-run stand for the fifth-wicket. The in-form Nair score his second fifty of the game, collecting 12 fours in his 123 ball knock.
Wickets of Nair and Shreyas Gopal in the final session would have made Rest of India feel a bit better after toiling through the day.