Gayle was unbeaten on a punishing 87 and Ganga was 59 not out at stumps, taking the tourists to 151-0 in reply to Pakistan's first-innings total of 357 on the second day at the Multan Stadium on Monday.
The West Indies, 1-0 down in the three-match series after losing by nine wickets in the first Test in Lahore, now trail by 206 runs with all their wickets in hand.
Scorecard of Day 2
Gayle -- the player of the Champions Trophy in India earlier this month with 414 runs including three hundreds -- hit ten boundaries and a six during his 233-minutes at the crease and put the home bowlers into submission.
The 27-year-old Jamaican, who managed 34 and 11 in the first Test, cut loose after tea by hitting leg-spinner Danish Kaneria for two successive boundaries to reach his half-century.
He treated Mohammad Hafeez with the same disdain, pulling the off-spinner for a huge six over mid-wicket and then driving two consecutive boundaries to stamp his authority.
Ganga, who played second fiddle to Gayle, reached his eighth Test fifty when he drove paceman Umar Gul for his ninth boundary to add to the home team's problems.
Earlier fast bowler Jerome Taylor took 5-91 -- his second five-wicket haul in nine Tests -- and Corey Collymore posted (2-67) to stop Pakistan from hitting a big score after they resumed at 263-4.
The 22-year-old Jamaican Taylor bowled his heart out on a lifeless pitch and was rewarded as the West Indies took the last six Pakistan wickets for 88 runs.
The tourists started with the second new ball and got an early result in the third over, when Taylor produced a sharp outswinger to find an edge off Inzamam's bat to wicket-keeper Denesh Ramdin.
Inzamam failed to add to his overnight score of 31.
The West Indies could have snared Malik in the next over, but Brian Lara grassed a low catch when the batsman was on 14.
Dwayne Bravo at third slip let Malik off again four runs later, with Collymore the unlucky bowler on both occasions.
Collymore, who bowled unchanged for 15 overs, finally forced an edge off Malik to third slip, where Bravo held a superb left-handed catch. Malik hit seven boundaries in his 42.
The 28-year-old Barbadian then dismissed Kamran Akmal (17) with another slip catch to Bravo to leave Pakistan at 333-7.
Taylor returned for his second spell to trap Shahid Nazir leg before for seven but Abdul Razzaq and Gul defied the West Indian bowling for 40 minutes. Taylor changed ends to dismiss Gul (seven) with another slip catch.
Last man Danish Kaneria was run out for nought, leaving Razzaq unbeaten on 16.