Resuming the second day on 261 for three after Atharva Taide's century and Yash Rathod's 93, Vidarbha rode on Nair's innings to post a big first-innings total.
In reply, Karnataka were 98 for two at stumps with Ravikumar Samarth and Nikin Jose batting on 43 and 20, respectively. The visitors trailed by 362 runs.
Vidarbha lost Akshay Wadkar (16) for the addition of just 23 runs to their overnight total, and were 319 for five, when Mohit Kale (16) was dismissed by Hardik Raj.
Nair and Aditya Sarwate (26) added 55 runs before the latter was dismissed by Vidwath Kaverappa, who picked up four wickets in all while giving away 99 runs.
Kaverappa's victims also included the all-important wicket of Nair, who fell short of his 19th first-class hundred by 10 runs.
Karnataka began their response on a jittery note, losing skipper Mayank Agarwal (0) to Aditya Thakare with just four runs on the board.
A 59-run partnership between opener Ravikumar Samarth (43 batting) and KV Aneesh (34) steadied the innings but Yash Thakur got rid of Aneesh with the score reading 63. As the match progresses, Vidarbha holds a strong position with a substantial lead. Karnataka faced an uphill task to overcome the deficit and make comeback in the knockout match.
Brief scores: Vidarbha 460 (Atharva Taide 109, Yash Rathod 93, Karun Nair (90); Vidwath Kaverappa 4/99) leads Karnataka 98-2 (Ravikumar Samarth 43 batting; Yash Thakur 1/22) by 362