Yousuf continued his prolific form with an undefeated 120 as Pakistan reached the interval on 308 for five, a lead of 74 runs with two sessions remaining.
Leading the three-match series 1-0 after a nine-wicket victory in Lahore last week, the hosts made 357 in the first innings before the visitors responded with 591, including a magnificent 216 from captain Brian Lara.
Pakistan were progressing steadily but suffered a setback in the penultimate over before the break when Shoaib Malik played on to his stumps from a Daren Powell delivery after batting for 48 minutes for his four runs.
Malik was the third wicket to fall in the session with Imran Farhat run out for 76 and captain Inzamam-ul-Haq dismissed for 10 runs.
Despite his flowing innings, Yousuf was lucky to survive at least two very close leg before appeals from Jerome Taylor and Corey Collymore, who examined the batsmen with the second new ball.
He was also dropped on 108 by Runako Morton at second slip off Powell, who bowled his best spell of the match.
Yousuf equalled the record of Sir Vivian Richards and Sri Lanka's Aravinda de Silva in completing his seventh century of the year -- his second of the series after a 192 in Lahore.
The elegant right hander has accumulated 1,491 runs in ten Tests this year.
He completed his 21st century from 153 balls with 13 fours by deftly flicking Taylor down to fine leg.
Opener Farhat was also dropped on 76 when Daren Ganga spilled a chance at silly point off Chris Gayle.
However, he was run out in a comical mix-up with Yousuf in the next over after Shivnarine Chanderpaul brilliantly stopped a powerful cut at point and made a quick return to the keeper.
His 76 came from 231 balls with nine fours to follow up on his first innings score of 74.
Brian Lara took the second new ball and Taylor struck by trapping Inzamam straight in front, continuing a poor run of form for the veteran batsman, who has not failed to pass fifty in his last five Tests.
Pakistan 357 and 308 for 5 (Mohammad Yousuf 120 n o, Imran Farhat 76, Younis Khan 56; Taylor 2 for 62, Darren Powell 1 for 34) Vs West Indies 591 (Brian Lara 216, Chris Gayle 93, Darren Ganga 82, Dwayne Bravo 89; Danish Kaneria 5 for 181)