Gayle made a well-constructed 124 but West Indies fell 22 runs short of an imposing Pakistan total of 303 for six in the final game of the three-match series.
The home side were bowled out for 281 in 49.3 overs, seamer Abdul Razzaq [ Images ] finishing with figures of four for 45.
It was Razzaq's second four-wicket haul of the series but Gayle gave the home supporters something to cheer about with his 11th hundred in hot and humid conditions.
Gayle kept the home team in touch with the victory target but his dismissal off the first ball of the 46th over sparked a lower order collapse as West Indies lost their last four wickets for just 31 runs.
West Indies suffered their second successive one-day clean sweep following a 5-0 drubbing by South Africa [ Images ] and have lost 12 of their last 13 limited-overs internationals since winning the ICC [ Images ] Champions Trophy [ Images ] in England [ Images ] last September.
Sunday's loss was the Windies' ninth in a row, the longest losing streak in their history, while Pakistan have won their last seven matches.
Gayle's well-paced hundred, which included 13 fours, kept the home side in the hunt until the 46th over when he was caught in the covers by captain Younis Khan [ Images ] off Shabbir Ahmed [ Images ], leaving West Indies to get 54 runs in 29 balls.
Gayle did not get enough support from the other batsmen as Wavell Hinds (35), captain Shivnarine Chanderpaul [ Images ] (33) and Runako Morton (27) all failed to go on after solid starts.
Earlier, Shahid Afridi [ Images ] smashed a sparkling 56 from just 30 balls, hitting six fours and two sixes in his 26th one-day half century as Pakistan made West Indies captain Chanderpaul rue his decision to field first.
After Afridi's fireworks, Yasir Hameed [ Images ] (41), Bazid Khan (66), Yousuf Youhana (50) and Younis (40) batted solidly and wicketkeeper Kamran Akmal smashed the last three balls of the innings from left-arm seamer Ian Bradshaw for six to lift Pakistan past 300.
Pakistan 1st innings
Y. Hameed c Browne b Collins 41
S. Afridi c Bravo b Collymore 56
B. Khan b Collymore 66
Y. Youhana c Morton b W. Hinds 50
Y. Khan c Morton b Bradshaw 40
A. Razzaq c Browne b Bradshaw 18
K. Akmal not out 24
Naved-ul-Hasan not out 0
Extras (lb-5 w-3) 8
Total (for 6 wickets, 50 overs) 303
Fall of wickets: 1-87 2-107 3-203 4-251 5-274 6-285
Bowling: Collins 10 - 0 - 49 - 1 (w-1), Bradshaw 10 - 1 - 78 - 2 (w-1), Collymore 10 - 0 - 51 - 2, Bravo 6 - 0 - 43 - 0, Gayle 10 - 0 - 54 - 0, W. Hinds 4 - 0 - 23 - 1 (w-1).
West Indies 1st innings
C. Gayle c Y. Khan b Ahmad 124
W. Hinds c Akmal b Razzaq 35
R. Sarwan c Y. Khan b Razzaq 4
S. Chanderpaul c Ahmad b Malik 33
R. Morton c Ahmad b Malik 27
D. Smith lbw b Razzaq 0
D. Bravo b Naved-ul-Hasan 16
C. Browne b Naved-ul-Hasan 11
I. Bradshaw c Hameed b Razzaq 13
P. Collins lbw b Naved-ul-Hasan 0
C. Collymore not out 0
Extras (lb-4 nb-6 w-8) 18
Total (all out, 49.3 overs) 281
Fall of wickets: 1-90 2-96 3-171 4-220 5-225 6-250 7-263 8-277 9-279 10-281
Bowling: Naved-ul-Hasan 9 - 1 - 48 - 3 (nb-3), Ahmad 10 - 1 - 64 - 1 (nb-2 w-2), A. Khan 10 - 0 - 44 - 0 (nb-1), Razzaq 6.3 - 0 - 45 - 4 (w-1), Afridi 6 - 0 - 35 - 0 (w-1), Malik 8 - 0 - 41 - 2 (w-3).
Result: Pakistan won by 22 runs