Wasim Jaffer hit his 10th Test half-century as India extended their second innings lead over Pakistan to 301 runs on day four at Kolkata.
Misbah-ul-Haq made a career-best 161 not out as Pakistan added 98 to their overnight total, but only Mohammad Sami (38) offered any support as Younus Khan's team were bowled out for 456.
Part-time spinner VVS Laxman broke the defiant 91-run stand between Sami and Misbah when the number eight holed out to Jaffer at mid-off.
Off-spinner Harbhajan Singh wrapped up his 20th five-for with the wickets of Shoaib Akhtar (duck) and Danish Kaneria (duck) before Jaffer (56) then picked up where he left off in first innings.
The first innings double-century maker put on 75 for the fall of the first wicket with Dinesh Karthik (28).
Despite both openers falling to leg-spinner Danish Kaneria, Mahendra Singh Dhoni (28 not out) and Sourav Ganguly (24 not out) put India in complete control of the match, closing on 141-2.
The hosts won the first Test in Delhi by six wickets and have the chance to seal the series with a speedy declaration on a deteriorating pitch on Tuesday.
They won the One-Day International series 3-2 in November and have dominated so far in Kolkata.
Watch all the action from a critical final day live on Sky Sports 2 from 4.30am on Tuesday.