Marnick Vermijl's eighth minute strike gave Championship side Preston victory over Watford at Deepdale with the defender on-loan from Sheffield Wednesday netting from close range.
Scott Sinclair struck a hat-trick for Villa, who had to level three times against their fourth-tier opponents, and Jermain Defoe also got a treble to help Sunderland chalk up a 6-3 win over Exeter City at The Stadium of Light.
Leicester City and Newcastle United were also among the goals with 4-1 wins away to third-tier Bury and at home to Northampton Town respectively, while Bournemouth thrashed another bottom division team Hartlepool 4-0 away.
Top-flight Stoke City, West Bromwich Albion and Crystal Palace were also taken to extra time before prevailing in their second-round clashes with lower league opponents.
Stoke won 8-7 on penalties at fourth-tier Luton Town after the game finished 1-1 in 120 minutes and West Brom prevailed 5-3 over third-tier Port Vale in a shootout following a 0-0 draw.
Palace eventually triumphed 4-1 after an extra 30 minutes having been held 1-1 at home by third-tier Shrewsbury Town.
The other two Premier League sides in action on Tuesday went through with Swansea City beating bottom division York City 3-0 while Norwich City edged second-tier Rotherham United 2-1 away.
Third-tier Barnsley host Everton on Wednesday.
(Reporting by Ken Ferris, editing by Pritha Sarkar)
