Saints' away game against Newcastle Falcons has been switched to St James' Park for an occasion that has been dubbed The Big One.
Jim Mallinder's men will travel to the home of Newcastle United on March 24, with the Aviva Premiership match kicking off at 5.30pm.
A varsity match between Newcastle University and Northumbria University will be played at 3pm.
St James’ Park, which has a capacity of 52,000, successfully staged three matches during Rugby World Cup 2015.
The stadium has also hosted three Super League Magic Weekends and will be the venue for the 2019 European Champions Cup and Challenge Cup finals.
Mick Hogan, managing director of Newcastle Falcons, said: “The Big One promises to be a major rugby occasion for the entire region to really get behind with adult tickets starting from just £10 and juniors from £5.
"We have set ourselves a target of 20,000 tickets sold for what will be a great day at a fantastic venue, one which has already shown itself to be more than capable of hosting top rugby events."
Falcons director of rugby Dean Richards also spoke of his excitement at The Big One.
“St James’ Park is an incredible stadium and this is a fantastic opportunity for us to take a game there," Richards said.
“The passion for sport in our region and the commitment from the public in supporting major sporting events is second to none, and it will be a memorable day which people will want to be part of.
"I was working at Harlequins when they began a similar initiative of playing a game at Twickenham every season, and they really are great occasions.”
The Big One will raise funds and awareness for Doddie Weir’5 Discretionary Trust, following the recent Motor Neurone Disease diagnosis of the Falcons and Scotland great.