Holders Liverpool were held to a 2-2 home draw by Wolverhampton Wanderers in a breathless FA Cup third round tie at Anfield on Saturday after Newcastle United were dumped out by third-tier Sheffield Wednesday.
However, Premier League sides Tottenham Hotspur, Leicester City, West Ham United and Southampton all reached round four.
Newcastle, who sit third in the top flight, fell two goals behind as League One (third-tier) side Sheffield Wednesday's Josh Windass netted twice in the second half.
Substitute Bruno Guimaraes pulled one back for Newcastle in the 69th minute when he tapped in from close range after goalkeeper Cameron Dawson kept out Chris Wood's initial effort from a corner, but it was little more than a consolation.
The world's oldest football tournament has a reputation for upsets and Nottingham Forest, who made 11 changes from the side that beat Southampton 1-0 in midweek, went out after slumping to a 4-1 defeat at second-tier strugglers Blackpool.
Bournemouth's torrid run since they returned from the World Cup break continued with a 4-2 loss at home to Championship leaders Burnley, with the Cherries suffering their fifth consecutive defeat in all competitions.
Meanwhile, fifth-tier Wrexham beat second-tier side Coventry City 4-3 in a thriller to reach the fourth round.
Liverpool went behind after goalkeeper Alisson passed the ball straight to Goncalo Guedes who fired home but they levelled as Darwin Nunez volleyed into the net on the stroke of halftime.
Mohamed Salah then made the most of a misdirected Toti header to slot past Matija Sarkic but Wolves substitute Hwang Hee-Chan forced a replay as he slotted through Alisson's legs.
The visitors thought they had a winner when Toti flicked the ball into the net but his effort was controversially ruled out for an offside spotted by the linesman in the build-up.
Tottenham Hotspur striker Harry Kane moved to within one goal of the club's record scorer Jimmy Greaves as his strike in a 1-0 win over Portsmouth took his tally to 265.
"I try to not think about it. Sometimes you can think too much," Kane said. "I feel in good form and I feel fit. My mindset is to help the team and hopefully the goals will come."
