The Brian Meehan-trained colt (12-1) dominated the 31-strong field to win by two lengths from Carry on Deryck.
Veteran jockey Joe Fanning won a first Group One race on 25-1 shot The Last Lion in the Middle Park Stakes.
Brave Anna won the Cheveley Park Stakes at the same price, beating stablemate Roly Poly (11-2) by a short head.
Odds-on favourite Lady Aurelia faded badly to finish third as trainer Aidan O'Brien claimed his first victory in the race.
In the Cambridgeshire, Fortune, successful on Pipedreamer in 2007, made the most of his draw on the stands side to grab the rail where it mattered and take the lead in the final furlong.
Very Talented (11-1) was a length behind Godolphin stablemate Carry on Deryck (20-1), with last year's winner Third Time Lucky (14-1) staying on well for fourth.
Fanning has had more than 2,000 winners but victory on The Last Lion in the Middle Park Stakes - on his 46th birthday - will be one of the most memorable.
He gave the Mark Johnston-trained colt the rein to roll from the start and the two-year-old was not for passing as he won by three-quarters of a length from Gimcrack winner and favourite Blue Point (11-10).
Fanning said: "I've ridden a lot of Group Twos and Threes, but never a Group One so it's nice to finally nail that one."
BBC racing correspondent Cornelius Lysaght on the Middle Park Stakes
Plenty won't have heard of the Irishman whose first winner came over hurdles so long ago (1989) that Peter Scudamore was champion jump jockey and Mrs Thatcher was prime minister.
He has built a fine reputation as the winner of more than 2,000 races, many for Mark Johnston, who has described probably his most regularly used rider as "worth his weight in gold".
Fanning isn't stopping yet, but had this outstanding judge of pace on front-runners, the style favoured by so many of Johnston's horses, completed his career without a top-level win it would have been a notable omission on his CV. That won't now happen.
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Spark Plug charged up the near-side rail to give jockey Jimmy Fortune his second win in the Cambridgeshire at Newmarket.