Roberto Martinez's side, who were without Romelu Lukaku, struggled to produce any consistent attacking threat in Germany and were subjected to a third defeat in five warm-up games as Paderborn punished some poor second-half defending.
Everton took the lead early in the game through young striker Chris Long, but things went downhill from there as the Premier League side crumbled to a second successive 3-1 defeat, having lost by the same scoreline to Celta Vigo on Wednesday.
Long's strike came after just 12 minutes as the 19-year-old received a pass from Leighton Baines, spun away from his marker and lashed the ball into the top corner.
Everton would have hoped to build on that good start but were only ahead for a minute as Paderborn equalised from the penalty spot.
Moritz Stoppelkamp made no mistake from 12 yards after Tim Howard was adjudged to have felled striker Stefan Kutschke on the edge of the area.
After going in level at the break, Everton went close to taking the lead again through a Baines free-kick.
Yet substitute Marvin Ducksch duly put Paderborn ahead for the first time in the 68th minute, albeit with a touch of fortune.
Marc Vucinovic created an opening for a shot on the edge of the penalty area but skewed his effort onto the head of Duksch, who converted via the crossbar at the back post.
With 15 minutes to go the game was over as Howard parried Mahir Saglik's effort into the path of Daniel Bruckner, allowing the latter to convert from 10 yards.
Martinez will now aim to lift his troops ahead of Everton's opening Premier League fixture at newly promoted Leicester City on August 16.