The 35-year-old went around the De Vere Slaley Hall in an even six birdies against no bogies to lead by two shots over Andrew Coltart and Jamie Spence, each of whom carded 68s.
Lee is searching for his first win on the European Tour. Having played the tour on a full-time basis for three of the last four years, his best finish to date is a tie for fifth at last years BMW International Open.
This season, he has played decent golf. Despite missing the cut at the last three events which he has played, the Englishman chalked up an eighth-place finish in Aprils Argentina Open.
Thursdays 66 marked his best score in over a month.
Likewise, Spence has to go back to Marchs Dubai Desert Classic to find the last time he posted a 68.
The two-time winner on the European Tour has either missed the cut or withdrawn from seven of the 11 events he has entered this year.
On the flip side, Andrew Oldcorn ' winner of this years Volvo PGA Championship ' is finding a resurgence to his golf game.
Wednesday, the Scot posted an opening round of 3-under 69 to be tied with four others, including Greg Turner, Roger Chapman, Bradley Dredge and Scott Gardiner, while young Justin Rose sits in joint ninth after a 70.
Defending champion Lee Westwood had his share of problems on Thursday.
Starting on the back nine first, the five-time winner on last seasons European Tour recorded three double-bogies and three bogies over his last nine at Slaley Hall to end with a nine-over 81.
Full-field scores from the Great North Open