It will be the first time a European club fixture has been played at the Millennium Stadium, already the home of the FA Cup, Community Shield, Worthington Cup, the Nationwide League Play-Offs and the Welsh international soccer side, and will be the second of three big fixtures at the ground in the final week of August.
The Welsh rugby team host current Grand Slam holders, and World ranked No 1 side, England at the Millennium Stadium on Saturday, 23 August and then entertain Scotland at the same venue seven days later in what will be the final warm-up match for Steve Hansen's side prior to the Rugby World Cup in Australia.
"We are delighted to have come to an agreement with TNS to host what will be the biggest game in their proud club's history," said Millennium Stadium manager Paul Sergeant.
"It is going to be a busy week for us at the Stadium, although we have turned around the pitch from soccer to rugby in far less time than the day and a half we will have between the UEFA Cup tie and the international friendly against the Scots.
"More importantly, this fixture demonstrates the truly national status of the Millennium Stadium. No sooner had TNS found themselves drawn against an English Premiership side than they thought of playing the fixture at the biggest and best home venue of any team in Wales.
"Cardiff may be a few hours drive away from Llansantffraid, but I am sure the football fans of south, as well as mid and north Wales, will come out and support TNS in this great fixture."
Kevin Keegan's Manchester City side contain many great players, some of who have already played at the Millennium Stadium. Robbie Fowler had the distinction of scoring the first club goal at the Millennium Stadium when he captained Liverpool to victory in the Worthington Cup final in 2001.
City's summer signing David Seaman became almost a regular at the Millennium Stadium while with Arsenal, including picking up an FA Cup winners medal in Cardiff against Chelsea in 2002 and Southampton in May this year.
But TNS are no strangers to the sporting fields at Cardiff Arms Park. They will become only the second club side to play at the old National Stadium, Cardiff Arms Park ground and the Millennium Stadium in August.
Cardiff City won the Welsh Cup on the old home of Welsh rugby and football before going on to clinch the Nationwide League Division Two Play-Off title last month at the Millennium Stadium.
TNS, meanwhile, also played in a Welsh Cup Final at the Arms Park and will break new ground at the Millennium Stadium in the Uefa Cup in August.
"This is great news for TNS, the Welsh Premier League and Welsh football as a whole. Our players and management are really excited at the prospect of playing at the greatest soccer stadium in the UK against one of England's finest teams, managed by a footballing legend like Kevin Keegan" said Mike Harris, chairman of TNS.
"As soon as we heard the draw we knew we had to do something special with our home fixture to do justice to the occasion. There could be no better setting than the Millennium Stadium.
"We did ask Manchester City if they would consider switching the fixtures around, but they told us they wanted to retain the first leg at their new home. Nevertheless, I'm sure there will be enough interest in the return leg to capture a big crowd at the Millennium Stadium.
"As well as giving our players, management team and fans a great night out, this move will also ensure the spotlight falls firmly on the ambitions of the leading clubs in the Welsh Premier League who want to see the quality of our product grow."
A policy on ticket prices and availability will be determined over the weekend and details released on Monday.