The match remained in the balance after Pakistan were set 355 to win, with Jack Leach's crucial wicket preventing the momentum from fully shifting in favour of the hosts as the sun set in Multan.
Imam-ul-Haq had looked composed and comfortable at the crease and had already survived a scare when he was caught in the slips by Joe Root from a thick edge off Leach, in what could prove a decisive breakthrough.
The batter remained at the crease with his head bowed over his bat in disbelief at his decision to go for the drive, which left England needing just six more wickets to win the series.
He had already been given a reprieve just before the wicket, when England elected not to review for a caught behind from Imam - then on 54 - only for DRS to show that Mark Wood's delivery had clipped the bat on the way through to the wicketkeeper.
Leach's scalp was the only wicket to fall in the final session and changed the fortunes of a spin attack who had bowled 37 overs - largely without troubling the Pakistan batters.
Ben Stokes had elected to introduce the extra seam option in Wood for the second Test and was vindicated for his decision, with the first three Pakistan wickets falling to the quick bowlers in the second session on day three.
However, the spinners were re-introduced after the break to little effect, with both Imam and Saud Shakeel offering up no chances, despite the deck having turned from the outset and debutant Pakistan leg-spinner Abrar Ahmed finishing England's second innings with 11 match wickets.
James Anderson made the first breakthrough after lunch with a perfect delivery that just moved enough off the pitch to clip the stumps and bowl stand-in opener Mohammad Rizwan for 30.
Imam had been to hospital for a scan on a hamstring injury so did not open the batting, with wicketkeeper Rizwan taking his usual spot. However, his introduction further down the order proved more problematic for England as he settled against the older ball.
Ollie Robinson claimed the key wicket of Pakistan captain Babar Azam with a ball that jagged back onto the stumps, after the batter played an ill-judged leave.
Wood then claimed his first wicket of the session, sending Abdullah Shafique's off-stump flying out of the ground from a skidding delivery after the opener had made 45.
Pakistan had been reduced for 83 for three but rallied with a mammoth 108-run stand for the fourth wicket to keep their hopes of levelling the series alive.
Earlier in the day, Harry Brook became the first centurion of the Multan Test, as England set Pakistan a target of 355 to win - his milestone coming from 137 balls.
Stokes was out for 41, but not before equalling Brendon McCullum's record for the highest number of sixes in Test cricket, and was caught in the deep trying to edge past the current England head coach's total.