Salt's unbeaten 141, after reaching three figures in a record 39 balls, and Jos Buttler's 83 decorated England's extraordinary total of 2-304, which included 18 sixes and 30 boundaries on Friday evening (Saturday AEST).
South Africa responded with resolve but were 3-64 after the powerplay and lost captain Aiden Markram for a team-high 41, off 20 balls, in the eighth over when the result became inevitable. The Proteas were then all out for 158 in the 17th over.
The three-match series now goes to a tiebreaker on Sunday in Nottingham.
The Proteas chose to bowl first in hope of using the moisture in the air, but all they caught was lightning from openers Salt and Buttler at their home club ground.
Salt clobbered the game's first three deliveries to the boundary off Marco Jansen but was soon overtaken by Buttler.
A fourth consecutive boundary brought up Buttler's 50 in 18 balls, the third fastest half-century for England.
He and Salt crashed 100 in the powerplay with a ball to spare, only the third time that's been done in a men's T20.
Buttler was on 83 from 30 balls and had Liam Livingstone's fastest England T20 century in 40 balls in his grasp. Then he hit straight to the fielder at deep square leg at 1-126 in the eighth over and Old Trafford rose to applaud.
Salt reached his 50 in 19 balls, one more ball than Buttler, but went on to break Livingstone's fastest record by one, reaching his ton in 39 deliveries.
The century was Salt's fourth for England. No other Englishman has more than one, and only Glenn Maxwell and Rohit Sharma -- five apiece -- have more T20 hundreds.
Salt's hundred came in a 23-run over bowled by Kagiso Rabada, who overstepped twice and bowled wide twice.
Salt passed his and England's highest T20 score of 119 from December 2023, and survived being out caught on 126 because Kwena Maphaka stepped on the rope at long-on, giving up Salt's sixth six.
England arrived at the last over needing 16 runs to break 300 and ultimately got there thanks to another no ball by Rabada. His 70 runs conceded were the most by a South African in men's T20s.
The only higher totals were Zimbabwe's 4-344 against Gambia in 2024 and Nepal's 3-314 versus Mongolia in 2023.Â
England eclipsed the best total by an ICC full member, India's 6-297 versus Bangladesh in 2024.
Salt finished unbeaten on 141 from 60 balls, with eight sixes and 15 boundaries. Captain Harry Brook was with him on 41 off 21.
The bowlers then feasted on the pressure on South Africa and Jofra Archer took 3-25, Sam Curran 2-11, Will Jacks 2-2 and Liam Dawson 2-34.
HIGHEST TOTALS IN MEN'S T20 INTERNATIONALS
4-344 Zimbabwe vs. Gambia, Nairobi, 2024
3-314 Nepal vs. Mongolia, Hangzhou, 2023
2-304 England vs. South Africa, Manchester, 2025
6-297 India vs. Bangladesh, Hyderabad, 2024
5-286 Zimbabwe vs. Seychelles, Nairobi, 2024
1-283 India vs. South Africa, Johannesburg, 2024
