Andrew Raitt, Nicolas Vanhootegem and Bradley Dredge share second place at 4-under-par 68.
Borrego broke into red figures early as he opened on the back nine at De Vere Slaley Hall Golf Club. He birdied his first three holes and added birdies at 15 and 17 to make the turn at 5-under 31.
The 30-year-old played steady on the inward nine but did not make birdie until the 349-yard fifth hole. Borrego ran home a 25-foot birdie putt to seal his round of 66.
Borrego won the Madeira Island Open in March but he has struggled since. He has missed two cuts out of four and also withdrew after an opening-round 77 at the Open de France. Borrego's finishes in the two cuts he made were a tie for 74th at the Deutsche Bank Open and a joint 56th at the Volvo PGA Championship.
The Spaniard thinks he has solved his problems and it all started on the tee.
'I had problems with my driver over the past few weeks but I have worked hard on it with Manuel Piero and it has paid off,' said Borrego. 'He has worked with me for about seven years and he knows my swing so it gave me a little bit of confidence.'
Dredge shared the lead as he played his final hole, the 18th at De Vere Slaley but he took a double-bogey six to drop into a share for the lead.
A double-bogey at the last is an all too familiar occurrence for Dredge as he carded the same score on the 18th hole in the final round of last year's event to drop out of the lead and fall into a tie for fourth.
'I bet my caddie Rick that I'd make par today so I'm a fiver down as well as being 4-over par for that hole for the last two times I've played it,' said Dredge. 'I'm going to have to make a big effort tomorrow. Maybe I'll go double or quits with Rick.'
Raitt was happy to finish in second place considering he was not even in the field at the beginning of the week. He was headed to the International Luxembourg Open on the Challenge Tour when he was notified by officials to take the place of Spains Jose Manuel Lara, who withdrew.
'I had just got off the boat in Calais when the call came through so I turned around and headed back,' said Raitt, who made it to the course two hours before his scheduled tee time. 'I've played here lots of times and I know the course well so there were no problems.'
Vanhootegem is riding a winning streak into the Great North Open. He won the Aa St Omer Open on the Challenge Tour last week, which ended a string of four missed cuts in a row on the big tour.
'I knew I needed just one good score, one good performance and my confidence would be back to where it should be and that happened in St Omer,' said Vanhootegem. 'I shot a 67 in the third round and then a 65 in the final round to win and Ive carried that on there this week.'
Roger Wessels, Marcus Knight, Gregory Havret and a pair of European Tour veterans - Des Smyth and Andrew Oldcorn - share fifth at 3-under-par 69.
Andrew Coltart, the 2001 champion, opened his title defense with a 1-over 73.