Northern Ireland striker scores both goals in 2-0 win as Arthur Masuaku sent off for West Ham. Elsewhere, Swansea City and Huddersfield Town will require replays against lower league opposition if they are to advance to the fifth round
Will Grigg's on fire as double sends West Ham packing out of FA Cup
Will Grigg scored twice as third-tier Wigan Athletic knocked 10-man West Ham United out of the FA Cup with a 2-0 win on Saturday.
Wigan have slumped down English football's ladder since winning the FA Cup in 2013 but the League One leaders rekindled memories of that run to Wembley as they reached the last 16 of this season's edition at the expense of David Moyes' Premier League side.
Northern Ireland striker Grigg made it five goals in as many cup ties this season when he put Wigan ahead in the seventh minute with a towering header past England goalkeeper Joe Hart.
To make matters worse for West Ham they were a man down four minutes into the second half when Arthur Masuaku was sent off, having appeared to spit at Wigan's Nick Powell.
Grigg made it 2-0 from the penalty spot shortly after the hour mark following Reece Burke's handball in the box.
Elsewhere struggling Premier League sides Swansea City and Huddersfield Town played out 1-1 draws with lower-division Notts County and Birmingham City respectively, leading to unwanted replays for teams whose priority is remaining in the top flight.
The Swans, bottom of the Premier League, took the lead when Luciano Narsingh scored just his second goal in 31 games for the Welsh club on the stroke of half time.
But fourth-tier County equalised in the 62nd minute through Jon Stead.
It was a similar story when a much-changed Huddersfield side, indicating manager David Wagner's preference for Premier League survival over a cup run, took an early lead against Birmingham through a Steve Mounie header.
Lukas Jutkiewicz, however, drew a Birmingham side battling to avoid relegation from the second-tier Championship level in the 54th minute.
Premier League Brighton & Hove Albion were also on the verge of a replay until Glenn Murray's 90th-minute goal secured a 1-0 win over Championship side Middlesbrough.
Saturday's early kick off saw Fousseni Diabate score twice on his Leicester City debut as the Premier League club won 5-1 at nearby East Midlands side Peterborough.
Any hopes third-tier Peterborough might create an upset lasted all of nine minutes, with Diabate's opening goal followed by two more from Kelechi Iheanacho that gave Leicester a 3-0 lead at half time.
Peterborough's Andrew Hughes pulled one back in the 58th minute before Diabate, who arrived at the King Power Stadium from French Ligue 2 club Gazelec Ajaccio this month, scored his second and Leicester's fourth in the 87th minute. Wilfred Ndidi made it 5-1 in stoppage-time.
But for Malian debutant Diabate's star showing, Nigeria international Iheanacho would have taken the headlines.
"It's a lovely competition to play in. It was a good team performance," Iheanacho told BT Sport.
Nottingham Forest's FA Cup run ended just one round after they knocked out holders Arsenal courtesy of a 2-1 defeat by Championship rivals Hull City.
The first of this weekend's all-Premier League ties saw Southampton beat Watford 1-0 as Jack Stephens marked his 24th birthday with a goal to ensure Javi Gracia's reign as Watford manager started with a defeat.
Fourth-tier Newport County will hope to pull off a classic "giantkilling" when they face eight-times winners Tottenham Hotspur at their Rodney Parade ground in South Wales later Saturday.
Liverpool play West Bromwich Albion at Anfield in the last of Saturday's ties.
Chelsea face Newcastle United in another all top-flight clash on Sunday when league leaders Manchester City continue their bid for an unprecedented quadruple of major trophies away to second-tier Cardiff.