Along with Manchester United's exit, the other big shock of the day came at Burton, where Burnley's awful cup competitions record under Sean Dyche continued with a 2-1 loss.
Kevin Long's header gave the Premier League team the lead, but League One Burton hit back through Liam Boyce, who then set up Jamie Allen for a late winner.
Penalties were needed in the all-Premier League tie at Molineux, with Danny Ward saving three spot-kicks after a goalless draw to book Leicester City a fourth-round berth at the expense of Wolves.
Callum Wilson scored a 94th-minute winner to secure a 3-2 home victory for Bournemouth against Blackburn Rovers, while Andros Townsend struck twice as Crystal Palace won 3-0 at West Brom.
Jordan Rhodes' hat-trick booked Norwich City's progression with a 4-3 thriller at Wycombe Wanderers, with 15-year-old Harvey Elliott making his Fulham debut in their 3-1 win at Millwall.
Middlesbrough scored all four of their penalties to edge through in a shootout after drawing 2-2 with Preston North End, while Blackpool are in the last 16 after a 2-0 home win against 10-man QPR.