FA Cup holders Arsenal beat Burnley 2-1 at the Emirates Stadium to book their place in the fifth round.
Arsenal, who won the competition in 2014 and 2015, handed Mohamed Elneny his debut and welcomed Alexis Sanchez and Francis Coquelin back into the starting lineup after spells on the sidelines through injury.
The Gunners took the lead on 19 minutes when Sanchez set up Calum Chambers to bend a shot into the top corner, but the Championship side hit back on the half-hour mark when Sam Vokes headed past David Ospina.
Sanchez restored their advantage early in the second half, crashing home Alex Oxlade-Chamberlain's cross, to secure progress.
Kelechi Iheanacho scored a hat trick as Manchester City thrashed Premier League relegation battlers Aston Villa 4-0 at Villa Park.
Iheanacho stabbed home the opener on four minutes after Villa keeper Brad Guzan had blocked Fernando's header.
The Nigerian doubled their advantage on 24 minutes, sending Guzan the wrong way from the penalty spot after Raheem Sterling went down in the area.
He added his third on 73 minutes following a poor backpass from Idrissa Gueye, and Sterling made it 4-0 moments later.
Liverpool's packed fixture slate will get even busier after a goalless draw with West Ham.
The result means the Reds' February schedule includes a replay in at Upton Park to go with three Premier League fixtures, a two-legged Europa League tie against Augsburg and the Capital One Cup final against Manchester City.
Liverpool came the closest to breaking the deadlock in the 75th minute, as West Ham keeper Darren Randolph made three saves in quick succession.
Randolph did well to keep out Christian Benteke, then Joe Allen and then Benteke again from close range.
Tottenham Hotspur eased into the fifth round with a 4-1 victory at Colchester United.
Colchester, who saw defender Alex Wynter stretchered off early on following a clash of heads and fellow centre-back Tom Eastman hurt in the same incident, fell behind on 27 minutes when Nacer Chadli fired home.
Spurs extended their lead through a deflected Eric Dier shot on 64 minutes before Marvin Sordell struck a post for the hosts. Chadli then headed home for his second of the game before Ben Davies scored an own goal shortly afterwards, making it 3-1.
Tom Carroll had the last word for the visitors, firing in off the underside of the bar from Chadli's cross.
Crystal Palace beat Stoke City 1-0 at Selhurst Park.
Wilfried Zaha put Palace ahead on 18 minutes, beating Stephen Ireland and Marc Wilson before sending the ball between keeper Jakob Haugaard's legs.
That proved enough to give the out-of-form Eagles a morale-boosting victory over the 2011 finalists.
West Bromwich Albion were held to a 2-2 draw by League One side Peterborough United after a flurry of late goals.
Saido Berahino gave West Brom the lead on 14 minutes, firing past Ben Alnwick from 25 yards after good work from Rickie Lambert.
Posh hit back through Shaq Coulthirst, a new signing from Tottenham, after a defensive mix-up on 79 minutes, but Berahino appeared to have settled it with a well-placed finish shortly afterwards.
On 86 minutes, though, Jon Taylor made it 2-2 to take the match to a replay.
Watford needed a late goal from Odion Ighalo to defeat Championship side Nottingham Forest 1-0 at the City Ground.
There was little threat from either side in the first half, with in-form Forest winger Jamie Ward going closest to breaking the deadlock with a shot that went just wide of Costel Pantilimon's post.
Substitute Ighalo won it for the Hornets in the 89th minute, though, after an error from Kelvin Wilson, ending an unbeaten run stretching back to Nov. 21 for the home side.
Bournemouth came from behind to beat League Two promotion hopefuls Portsmouth 2-1 at Fratton Park.
Portsmouth -- winners of the competition in 2008 -- took a surprise lead just before the break when Marc McNulty set up Gary Roberts to slide home.
The visitors hit back on 71 minutes when Joshua King headed home from a free kick, and Marc Pugh later bundled home the winner.
Shrewsbury Town booked their place in the fifth round for the first time in 25 years with a stunning last-gasp 3-2 victory over Sheffield Wednesday.
The Owls led 2-1 going into the last five minutes before Shrewsbury roared back with Shaun Whalley's equaliser followed by a Jack Grimmer winner deep into stoppage time.
Wednesday had twice taken a one-goal advantage through Lewis McGugan's brace either side of Jean-Louis Akpa Akpro pulling one back for the Shrews, who stunned their visitors in the closing minutes to complete a memorable win.
Toumani Diagouraga marked his first start for Leeds with a rare goal and a familiar booking as Steve Evans' side beat Bolton 2-1.
Souleymane Doukara put the Elland Road outfit in front early on but after bossing much of the match Leeds were forced into some late desperate defending.
Wanderers captain Darren Pratley netted for a fourth time in six games to pull a goal back before top scorer Gary Madine hit the post four minutes from time.
Chuba Akpom hit a hat trick for Hull City in their 3-1 win at Bury.
The on-loan Arsenal striker gave the 2014 runners-up a 14th-minute lead before converting a 57th-minute penalty.
The 20-year-old struck again 12 minutes later to claim his first treble in senior football, while Craig Jones claimed a consolation with four minutes left.
Ben Marshall and Tony Watt did their best to soften the blow of Jordan Rhodes' departure by firing Blackburn into the fifth round of the FA Cup courtesy of a 3-0 win at Oxford.
Watt, signed this week from Charlton and given the thankless task of replacing Rovers' star man, got off to a decent start with a debut goal while Marshall scored twice as Oxford's cup adventure was ended.
Matej Vydra scored twice as Reading beat League One side Walsall 4-0.
Losing semifinalists last season, the Championship side struck twice shortly before half-time against Walsall through Hal Robson-Kanu and Vydra.
Walsall offered little threat throughout and Reading added further goals in the second half from Danny Williams and Vydra, emphasising their dominance.
Information from the Press Association was used in this report.