Inkster, a two-time champion at Mission Hills Country Club, the course that has played host to this event since its inception in 1972, posted a 70 along with Penny Hammel, Liselotte Neumann, Carin Koch and 1998 Nabisco winner Pat Hurst.
Two-under-par 70 is the highest score for an opening-round lead at the Nabisco since the tournament was designated a major in 1983.
Dottie Pepper, the Nabisco winner in 1992 and 1999, recorded the fourth hole-in-one of her career on her way to finishing the day one shot back with a one-under 71. She is tied with Alison Nicholas, Michele Redman, Lorena Ochoa, Tina Barrett, Laura Diaz and Laura Davies.
Annika Sorenstam is among 10 players at even par, while defending champion Karrie Webb is three strokes off the pace after carding two birdies and three bogeys for a 73.
Inkster was two-under when she reached the tee of the par-three 14th. After she found herself between clubs at the 148-yard hole, Inkster decided to hit a soft seven-iron but pushed her ball right into the water hazard guarding the green. She wound up with a double- bogey to drop to even-par on the day.
She chose the seven-iron again for her approach to 16, this time leaving the ball 15 feet from the flag to set up a birdie. At 17, Inkster knocked a six-iron over the pin in the front but rolled in a 25-foot birdie putt to climb back to two-under par.
Inkster averted a minor disaster at the last when she sank a clutch par-saving putt after leaving her long birdie attempt 12 feet short.
Inkster, whose win here in 1984 marked her second professional victory and the first of her six major titles, felt that the conditions in Thursday's round were as difficult as she can remember.
'The wind was up, the greens were hard, the rough is up. It was extremely tough to get the right club in your hand,' said Inkster, who also won here in 1989. 'But for a major championship it should be tough, I mean, there is plenty of room to drive it out there. With thewind it just adds that degree of difficulty.'
Inkster, named to the Hall of Fame in 1999, is playing in her 17th Nabisco Championship.
Hammel and Neumann both had three-birdie rounds derailed by last minute bogeys, while Koch saw an early eagle negated by two bogeys down the stretch.
Koch enjoyed a strong start with birdies at the first two holes, then moved into the lead at four-under par when she holed her approach from 140 yards at the par-four sixth.
Although she three-putted for a bogey at the par-five 11th, Koch struck back with a 10-foot birdie putt at the 12th. However, poor tee shots at the 15th and 18th led to bogeys when she too had to tangle with the long grass.
'You just can't hit much more than a short iron out of it,' said Koch. 'I had played 13 holes of the practice round on Monday and then the pro-am yesterday and I hadn't been in the rough off the tee yet. I didn't really know what to expect when I hit it in there.'
Koch, who went 3-0 for the victorious European squad in her first trip to the Solheim Cup last October, is still in search of her first win on the LPGA Tour. She has finished as a runner-up six times since joining the tour in 1995.
Hurst experienced an up-and-down front nine, but was one of only 16 golfers in the 96-player field to birdie the par-five 18th on Thursday.
Pepper managed to put back-to-back bogeys behind her when she knocked a six-iron into the cup for an ace at the 164-yard fifth hole. Although she added birdies at six, seven and 11 to pull herself to up to four-under par, Pepper dropped three shots over the span of five holes on the way in to the clubhouse.
Sorenstam, who fired an LPGA record 59 on her way to winning her second straight tournament of the season at last week's Standard Register PING, needed at least a 69 on Thursday to tie LPGA mark for most consecutive rounds in the 60s with nine.
Webb, still looking for her first LPGA title of the season, cruised to a 10-shot victory over Pepper here a year ago. It was her second win in a major, and she went on to capture last season's U.S. Women's Open for her third major championship title.
Full-Field Scores from the Nabisco Championship