Miller brought up his century off 122 balls in the 48th over, after coming to the wicket inside the first ten overs in the fourth ODI.
Together with JP Duminy (43), the pair put on 90 for the fifth wicket as the hosts moved towards a defendable total in the five match series they led 3-0.
After reaching three-figures, Miller opened up and began to find the boundary with ease as the Proteas surged beyond the 250 run mark.
Miller ended the innings unbeaten on 130 from 133 balls with 11 fours and three sixes.
West Indian captain Jason Holder was inspirational in his role with the ball as he returned figures of 4/53 from his ten overs.
South Africa were in trouble early as they found themselves 32 for three inside the first seven overs.
Rilee Rossouw (4) was the first to depart, with Darren Sammy taking a diving catch at first slip off the bowling of Sheldon Cottrell.
Faf du Plessis also made four before returning to the changeroom, well caught behind by wicketkeeper Denesh Ramdin off the bowling of Holder.
Morne van Wyk looked good for his 18 from 24 balls, but chased a Cottrell delivery and edged through to Ramdin.
A brief period of recovery followed with a 44 run stand from 51 balls for the fourth wicket between Proteas captain AB de Villiers and Miller.
De Villiers (19), however, failed for the first time in the series when he edged to Ramdin off the bowling of Andre Russell as the Proteas were reduced to 76 for four.
It was then the turn of Duminy and Miller to attempt a recovery.
Duminy’s knock came to an end after 68 balls, when he was caught and bowled by Sammy as the batsman chipped the ball straight back towards the West Indian with South Africa left on 166 for five.
Farhaan Behardien was unable to cash-in, coming in with 13.2 overs remaining. Behardien was bowled by Holder for 12 to leave South Africa 196 for six in the 43rd over.
At the end, Wayne Parnell (12) was a spectator in a 63 run seventh wicket stand between he and Miller from 47 balls, as the hosts let loose at the climax of their 50 overs with the bat.