The 21-year-old showed the sort of sizzling form that once carried him to number one in the world amateur rankings as he opened a one-stroke lead over fellow Englishman Lee Slattery, Robert Karlsson of Sweden, Dane Soren Kjeldsen and Scot Marc Warren.
Fitzpatrick, who was within inches of claiming the first 59 in European Tour history at last month's Dutch Open, took advantage of ideal scoring conditions by racing to the turn in 31 at Woburn's Marquess Course.
He mixed an eagle at the par-five seventh with three birdies and a solitary bogey on the outward nine before making further inroads on par at the 13th, 17th and 18th.
Fitzpatrick has finished in the top three in three of his last seven outings and said the European Masters at Crans Montana in July proved a turning point in his season.
"I started hitting a fade in Switzerland," the rookie professional told reporters. "That was sort of the start of the run.
"It was a great day today. I hit it really nice and scrambled well when I needed to.
"I had a tough start to the season. I missed quite a few cuts in a row even though I thought I was playing alright," said Fitzpatrick.
"Now I'm playing decently and getting the results I've been looking for."
FREE TICKETS
The British Masters is back on the European Tour schedule for the first time in seven years and 14,625 fans turned up for the opening round, helped by free tickets being handed out.
"It doesn't get any better than that," said Fitzpatrick. "The crowd have been absolutely fantastic."
Former European number one Karlsson would have joined him on 64 but for a bogey five at the last hole.
Triple major winner Padraig Harrington and fellow Irishman Shane Lowry were among six players to start with a 66 while former world number one Luke Donald went round in 67.
Tournament host Ian Poulter was also well placed after shooting a 68. Lee Westwood, winner of the event in 2007, had a 69 and 2010 U.S. Open champion Graeme McDowell returned a 70.
"To win a British Masters would be very special," said Northern Irishman McDowell. "Outside of my Scottish Open win in 2008 and Wales Open win in 2010, I haven't won here in the United Kingdom.
"There is a special element of winning in front of the home fans. I'd dearly love a (British Open) Claret Jug of course but an event like the British Masters would come a close second."
(Editing by Toby Davis)
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