The 23-year-old from Banbridge clocked 15 minutes, 50.55 seconds to take almost three seconds off Duffy's 1996 mark of 15:53.47.
Mitchell was third in the British Milers Club event won by Louise Small of England in 15:42.47.
Irish Olympian Kerry O'Flaherty finished seventh in 16:32.56.
O'Flaherty said after the race that she sustained a grade two calf tear at the 1800m mark which required hospital treatment.
The injury could keep the Newcastle women out for a number of weeks.
Mitchell's time was over a minute inside her previous personal best for the distance.
The QUB athlete will now attempt to achieve Athletics Northern Ireland's Commonwealth Games consideration time of 15:39.00 before the 30 September deadline.
Meanwhile, Northern Ireland Commonwealth Games sprinter Leon Reid showed impressive early-season form as he clocked wind-assisted 100m times of 10.26 and 10.27 in Waterford on Saturday.
The 22-year-old, whose mother was born in Belfast, is hoping to switch international eligibility from Great Britain to Ireland and has joined Wexford club Menapians.
Reid won a European junior 200m silver medal for Britain in 2013 and also finished second in the same event at the European under-23s two years ago.
Queen's athlete Emma Mitchell broke Teresa Duffy's 21-year-old Northern Ireland 5,000m record at a meeting in Solihull on Saturday night.