Hopkins wrested the WBC, IBO and The Ring magazine titles from his 28-year-old opponent, who was making his fifth defense at the Bell Centre.
Hopkins (52-5-2) is the oldest fighter to take a major world belt, six months older than George Foreman when he took the heavyweight title with a victory over Michael Moorer in 1994.
The Philadelphia boxer weathered an early attack from his Montreal opponent before landing more punches and avoiding many of Pascal's power shots, jabbing intelligently and landing a number of right-handers.
Hopkins also taunted his younger foe, dropping to do press-ups before the seventh round.
Despite getting hurt in the 12th Round, Hopkins survived and did enough to win.
Hopkins was ranked as BoxRec's top light heavyweight; Pascal was second.
115-113, 116-112, 115-114
This bout was a rematch of their first fight five months earlier in which most ring experts thoughts Hopkins won. The bout was ruled a draw.
At 46, Hopkins became the oldest man to win a major world title.