Blue Square North side Northwich suffered a 3-1 defeat to League Two strugglers Lincoln in the FA Cup second-round clash at the Victoria Stadium.
Two goals in 15 minutes from Jamie Clarke ended Northwich's hopes after Matthew Bailey had cancelled out Chris Fagan's 18th-minute opener early in the second half.
Amongst the all-league clashes, the game of the day involved MK Dons and Exeter, the latter taking a 3-1 lead midway through the second half, but Paul Ince's side produced a stunning comeback to secure their place in the third-round draw, Jermaine Easter poaching the winner in a 4-3 victory in the 86th minute.
Notts County came from behind to beat League Two leaders Bournemouth 2-1, with Lee Hughes and Craig Westcarr on the scoresheet in the second half after Brett Pitman had given the Cherries a first-half lead at Dean Court.
Colchester, third in League One, had to wait until the 94th minute to crack League Two Hereford courtesy of John-Joe O'Toole's second goal for the club following his loan move from Watford.
League One Huddersfield also beat League Two opposition in Port Vale courtesy of Nathan Clarke's 12th-minute effort.
Gillingham beat Burton Albion 1-0 with Curtis Weston scoring the only goal in the 69th minute at the Priestfield Stadium.
After taking a 3-0 lead, Southampton survived a late rally against Northampton at Sixfields Stadium as the home side pulled back two goals late on.
League One's bottom club Tranmere will need a replay to overcome Aldershot after being held to a goalless draw at Prenton Park.
Brentford edged past Walsall 1-0 at Griffin Park in an all-League One affair courtesy of Leon Legge's 13th-minute winner and League Two rivals Accrington and Barnet will have to replay after their 2-2 draw - John O'Flynn scoring a 95th-minute penalty for the Bees to send them back to Underhill.
Copyright (c) PA Sport 2009, All Rights Reserved.
Do YOU want to write for GiveMeSport? Get started today by signing-up and submitting an article HERE: http://gms.to/writeforgms