Preston North End stepped in to sign the striker, paying £500,000. Fuller scored on his Preston debut, a 2–1 defeat at home to old club Crystal Palace, and soon became a vital team player. He had an explosive scoring rate, but unfortunately he suffered knee ligament damage in early December, which ended his season prematurely. He had scored 11 goals in only 20 appearances for the club. A fit again Fuller began the 2003–04 season on fire, including a run of six goals in five games, but his form tailed off as his knee troubled him once more. Despite this, he still scored 19 goals that season to become the club's top-scorer. Fuller handed in a transfer request in June 2004 to force through a move to a Premiership club.
Both Leeds United and Portsmouth then displayed their interest, however, Fuller's knee problems meant both clubs withdrew their offers after he failed medicals. However, Portsmouth manager Harry Redknapp was still keen on the Jamaican and Pompey negotiated a 'pay-as-you-play' deal with Fuller, meaning they would not lose a great deal of money should his recurring knee injuries force him to miss long periods of seasons. Fuller moved to Fratton Park in August 2004 for £1 million, after scoring 31 goals in only 63 appearances for Preston.