Khadiwale scored 136 off 193 balls with the help of 19 boundaries and a lone six, while Sangram Dilip Atitkar (78) and Ankit Bawne (80 not out) also made fine contributions with the bat to keep Maharashtra in the game.
H S Sharath and Syed Khaja Moinuddin picked up a wicket each for Karnataka.
Earlier resuming at the overnight score of 58 for one, Maharashtra were bundled out for a meagre 99 in their first innings in reply to Karnataka's 572 for nine declared.
Medium-pacer Abhimanyu Mithun scalped six wickets for 36 runs, while Stuart Binny picked up four for 37.
Following on, Maharashtra batsmen gave a better account of themselves in their second innings with Khadiwale and Atitkar sharing a 156-run opening stand.
After Atitkar's dismissal, Khadiwale joined hands with Bawne and the duo stitched 146 runs for the second wicket to take Maharshtra forward.
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At stumps on the penultimate day of the match, Maharashtra still trail Karnataka by 158 runs with eight wickets in hand.
Brief Scores:
Karnataka 1st Innings: 572 for nine decl in 158.5 overs
Maharshtra: 99 & 315 for two in 74 overs (Harshad Khadiwale 136, Ankit Bawne 80, Sangram Dilip Atitkar 78; H S Sharath 1/54).