Spinner Panesar, playing his first Test match since 2009, dispatched opener Mohammad Hafeez (22), captain Misbah-ul-Haq (12) and Younus Khan (1) in Abu Dhabi to leave Pakistan struggling on 54 for four with England looking well-placed to avenge their 10-wicket defeat in the series opener last week.
However, batsmen Asad Shafiq and Azhar Ali dug in, roared on by the team's passionate support as they put on an unbeaten fifth-wicket stand of 71.
Security problems have forced Pakistan to play home matches in the Gulf, but with more than a million Pakistanis living in the United Arab Emirates the Abu Dhabi crowd was firmly behind Misbah's men.
Pakistan's raucous supporters filled the stands, the attendance swelling after midday prayers. Every run brought exuberant cheers as England's bowling menace waned as the session end drew near.
Shafiq (35) and Ali (46) upped Pakistan's run rate from just 73 in the first 40 overs of the innings to 52 from the final 21 overs.
Their only real scare was when Kevin Pietersen fluffed a run-out opportunity, missing the stumps with Shafiq flailing in no-man's land as Pakistan attempted a quick single.
The afternoon had started brightly for Pakistan, who bagged England's final two wickets before openers Hafeez and Taufeeq Umar made a steady start to their second innings.
England then struck, Panesar drawing Hafeez forward as the batsman tried to block the anticipated turn, but the ball kept straight for a clear lbw.
Fellow spinner Graeme Swann came on at the other end and bowled Umar (7), the ball sneaking between bat and pad as Pakistan lost their second wicket without adding to their score of 29.
Panesar was not to be outshone, however. He bowled Khan with a turning delivery that clipped off-stump and then snagged Misbah lbw with a sliding ball that struck the Pakistan captain below the knee. Panesar ended the day on 3-44.
Earlier, Stuart Broad's unbeaten 58 had helped England achieve a 70-run first innings lead.
His knock was vital after Matt Prior and Ian Bell both disappointed with the bat, England losing their final five wickets for 120 runs.
For Pakistan, all-rounder Hafeez finished with 3-54, while Saeed Ajmal ended on 4-108.
