Gillingham provided the shock of the FA Cup third round so far as they dumped Premier League side Cardiff City out of the competition thanks to a 1-0 win.
Elliott List's late strike was enough to secure the third-tier side, who are 18th in League One, a memorable victory. Cardiff manager Neil Warnock made several changes for the trip to Priestfield Stadium but started two of his strongest attacking players in Callum Paterson and Bobby Reid up front.
Newcastle United survived an almighty scare, needing a Matt Ritchie penalty six minutes from time to draw 1-1 and salvage a replay against Championship side Blackburn Rovers. Bradley Dack's powerful header put Rovers in front at St James' Park before the hour mark but Rafa Benitez's men managed to scrape a replay at Ewood Park.
Meanwhile, Huddersfield were stunned by Bristol City as the midtable Championship side dumped David Wagner's men out of the cup thanks to Josh Brownhill's strike.
Crystal Palace were another Premier League side to have it tough against lower opposition, as League Two Grimsby came within four minutes of forcing a replay in a 1-0 defeat at Selhurst Park. Grimsby played 88 minutes with 10 men after David Fox was sent off in the early stages but they looked to have secured a replay until Jordan Ayew struck late on.
Frank Lampard's Derby County also secured a result against Premier League opposition, forcing Southampton into a replay after a 2-2 draw at Pride Park. Nathan Redmond's brace was quickly cancelled out in the second half thanks to two goals in three minutes from Jack Marriott and Tom Lawrence.
League One side Accrington Stanley inflicted further misery on Ipswich Town after a 1-0 win. Billy Kee's 76th-minute winner was enough to knock out Paul Lambert's team, who couldn't improve on the form which has seen them fall to the bottom of the Championship.
Everton squeezed past League Two leaders Lincoln City to win 2-1 at Goodison Park. Despite taking an early lead through Ademola Lookman and Bernard, Lincoln fought back through Michael Bostwick but couldn't find the equaliser as Marco Silva's side held on to advance.
Cesc Fabregas missed a penalty on what could be his final appearance for Chelsea as the Blues defeated Nottingham Forest 2-0 at Stamford Bridge. Alvaro Morata added the goals for boss Maurizio Sarri, who had to call upon Eden Hazard from the bench after an injury to England midfielder Ruben Loftus-Cheek.
Elsewhere, Championship sides Bolton Wanderers and Middlesbrough progressed after comprehensive victories over Walsall and Peterborough United respectively.
Third-tier Walsall took a 1-0 lead into the break at the Reebok Stadium but Bolton produced a second half fightback to eventually win 5-2. Britt Assombalonga scored twice for Middlesbrough as the home side also hit five in a comfortable 5-0 win.
League One leaders Portsmouth pulled off a surprise as an injury-time winner from Andre Green was enough to knock Championship promotion hopefuls Norwich City out of the cup.
In an all-Championship tie, seven-time winners Aston Villa were thrashed 3-0 by Swansea City. Courtney Baker-Richardson, Nathan Dyer and Jay Fulton were on target for the Swans at Villa Park.
Championship side Brentford edged League One outfit Oxford United in a 1-0 win while AFC Wimbledon grabbed a 90th-minute winner to defeat Joey Barton's Fleetwood Town 3-2 in an entertaining all-League One encounter at Highbury Stadium.
Earlier in the day, Ole Gunnar Solskjaer extended his winning start as Manchester United manager to five matches as the 12-time winners dismissed Championship side Reading 2-0 at Old Trafford. Juan Mata opened the scoring from the spot before Romelu Lukaku doubled the home side's advantage on the stroke of half-time.
Arsenal, meanwhile, made light work of League One Blackpool in a 3-0 win at Bloomfield Road despite arriving at the ground late after a fan had sat on the away team bus, blocking its route to the match. On the field, Joe Willock scored two and Alex Iwobi added another for Unai Emery's men.
Premier League strugglers Burnley made hard work of a 1-0 win over third-tier Barnsley in a match notable for a bizarre intervention by the video assistant referee (VAR) -- the system being used in nine of the 32 third-round ties.
Burnley were awarded a penalty for a foul on Matej Vydra before the interval but just as he was running up to take the spot kick, referee Simon Hooper indicated that the decision had been reversed by VAR because of an offside in the build-up.
Burnley manager Sean Dyche was left fuming but his mood improved when Chris Wood eventually sealed victory from the penalty spot in the second minute of stoppage time.
Brighton & Hove Albion beat Bournemouth 3-1 away in an all-Premier League affair with Anthony Knockaert, Yves Bissouma and Florin Andone all on target.
West Ham United's Marko Arnautovic was forced off due to a first-half injury in a 2-0 win over Birmingham City at the London Stadium. The Austrian forward scored the opening goal of the game before he was replaced by former England striker Andy Carroll, who wrapped up the match thanks to a second-half header.
Shrewsbury Town of League One held the Championship's Stoke City to a 1-1 draw, while West Bromwich Albion defeated 2013 winners Wigan Athletic 1-0 to advance to the fourth round.