Rovers will travel to St. James' Park on the week commencing Monday, 14th September. Full details will be confirmed shortly.
Supporters will not be able to attend the game due to Covid-19 restrictions. The round two draw was unseeded and regionalised, with northern and southern sections.
The two sides last met in the Emirates FA Cup in January 2019, with United winning 4-2 after a replay at Ewood Park following a 1-1 draw on Tyneside. Newcastle's last tie with Rovers in this competition came back in October 2011, with Blackburn winning 4-3 in Lancashire.
Rovers beat Doncaster Rovers 3-2 in the first round at the end of last month, with goals from Lewis Holtby, Joe Rankin-Costello and former Magpies man Adam Armstrong.
The winners of the second round tie will travel to Morecambe or Oldham Athletic after the third round draw was also made on Sunday.
That game would take place on the week commencing Monday, 21st September.
David Garrido and former Liverpool defender Phil Babb made the draws.
Second-round draw North: Burnley v Sheffield United, Burton Albion v Aston Villa, Bradford City v Lincoln City, Leeds United v Hull City, Everton v Salford City, Wolverhampton Wanderers v Stoke City, Rochdale v Sheffield Wednesday, West Bromwich Albion v Harrogate Town, Middlesbrough v Barnsley, Derby County v Preston North End, Newcastle United v Blackburn Rovers, Morecambe v Oldham Athletic, Fleetwood Town v Port Vale South: West Ham United v Charlton Athletic, Ipswich Town v Fulham, Oxford United v Watford, AFC Bournemouth v Crystal Palace, Leyton Orient v Plymouth Argyle, Southampton v Brentford, Bristol City v Northampton Town, Reading v Luton Town, Millwall v Cheltenham Town, Brighton & Hove Albion v Portsmouth, Newport County v Cambridge United, Gillingham v Coventry City
Third round draw Bradford or Lincoln City v Liverpool, Bristol City or Northampton Town v Burton Albion or Aston Villa, Morecambe or Oldham Athletic v Newcastle United or Blackburn Rovers, Reading or Luton Town v Manchester United, Derby County or Preston North End v Brighton & Hove Albion or Portsmouth, Ipswich or Fulham v Rochdale or Sheffield Wednesday, Manchester City v AFC Bournemouth or Crystal Palace, Millwall or Cheltenham v Burnley or Sheffield United, Chelsea v Middlesbrough or Barnsley, Wolverhampton Wanderers or Stoke City v Gillingham or Coventry City, Leicester City v Arsenal, West Bromwich Albion or Harrogate Town v Southampton or Brentford, Newport County or Cambridge United v Oxford United or Watford, Fleetwood Town or Port Vale v Everton or Salford City, Leyton Orient or Portsmouth v Tottenham Hotspur, West Ham United or Charlton Athletic v Leeds United or Hull City