Preston North End 1-1 (16-15 on pens) Fulham: Silva made to pay for wholesale changes
Fulham reached the semi-finals of the Carabao Cup last season but this term they exited in the third round.
Marco Silva made the full 11 changes and his side looked disjointed as a result.
Reiss Nelson scored his first goal for the Whites on his first start after Preston had gone in front.
However, Fulham were unable to push on after they equalised with Silva waiting until the 77th minute to make changes.
Timothy Castagne and Jorge Cuenca missed their spot kicks as Preston won 16-15 on penalties. It was the longest shootout in League Cup history, eclipsing the previous record set by Derby County and Carlisle in 2016 when the Rams won 14-13.
Rodrigo Muniz blazed an effort over the bar and was unable to convert the rebound from Harrison Reed's fierce strike which came off the crossbar.
Attention now turns to Saturday when they host Newcastle (15:00 BST) in the Premier League in a bid to get back to winning ways.