Jockey Sean Levey glided through the field to win the race by one and three one-quarter lengths.
Watch 66-1 Billesdon Brook win the 1,000 Guineas
Laurens was second, with Ryan Moore third on favourite Happily .
The trainer also finished last with Moore and Mendelssohn in the Kentucky Derby before the pair built the trip-up back across the Atlantic .
On Sunday, Moore was well placed into the final two furlongs on the 11-4 favourite, but was unable to quicken .
Charlie Appleby's well-fancied Soliloquy, ridden by William Buick, finished three and a one-quarter lengths back in sixth .
Chestnut filly Billesdon Brook, who was fourth when Soliloquy won over seven furlongs at Newmarket last month, came through from the outside to pass Fillies' Mile heroine Laurens .
Analysis by BBC horse racing correspondent Cornelius Lysaght
With her long odds, there will be an inclination to look for a fluky facet to Billesdon Brook's success but if, tell, Happily had won in exactly the same way, there'd be no such chats .
She won with a degree with authority and in a decent time- it didn't look like a fluke .
The importance of the win for a black jockey will be much discussed as will the fact that the owners- 23 friends calling themselves the Pall Mall Partners- are not the usual suspects; you don't necessarily have to be an Irish multi-millionaire or sheikh to win big in flat racing for once.