At the line, Encke held on to win by 3/4 length, adding Camelot's name to those of nine previous Guineas and Derby winners who failed in the 1 3/4-miles St Leger, the testing third leg of the English Triple Crown.
The Crown has not been won since Nijinsky turned the trick in 1970 and only 15 have accomplished the feat.
Encke, a Kingmambo colt, gave Sheik Mohammed's Godolphin racing its sixth St Leger winner, tied for second on that list with the 17th Earl of Derby and the third Aga Khan.
The most successful owner in the last of the English Classics was the ninth Duke of Hamilton, who sent out seven winners between 1786 and 1814.
The win also was a triumph for the Godolphin's up-and-coming duo of trainer Mickael Barzalona and trainer Mahmood Al Zarooni, who brought Encke to Doncaster off a third-place finish in the Group 2 Great Voltigeur Stakes at York Aug. 22.
Saturday, Barzalona got Encke revved up outside the leaders with just under 2 furlongs to run down the long Doncaster straight. He quickly opened up 3 lengths on the field while Joseph O'Brien, aboard Camelot, was caught behind traffic and looking for room.
Once O'Brien got Camelot free, he came with a courageous run but had been left with too much to do.
Michaelangelo was a non-threatening third.
The race went in 3:03.81 over ground rated good to soft.