A fourth minute surprise goal by Wanderers' Henrik Pedersen was enough to give his side three precious points at the Reebok Stadium.
The Dane's perfectly weighted lob from the by-line went over defenders' heads and into the net.
Meanwhile Newcastle's away form seems likely to deny them a Champions League place.
Bolton manager Sam Allardyce stood by the team that gave a spirited performance in their 2-1 defeat at Arsenal last time out.
Sir Bobby Robson made three changes to the team that beat Mallorca 3-0 in the UEFA Cup with Craig Bellamy, Lee Bowyer and Steven Taylor all being given a start.
A lively start from the home team put Newcastle on the back foot and the game was only four minutes old when Wanderers took the lead.
Pedersen almost on the by-line robbed debut defender Taylor of the ball and when the Dane put over the measured cross the Magpies defence could do nothing but watch the ball fall into the net.
Newcastle almost pulled it back in the 14th minute when Alan Shearer's bicycle kick was well saved by Jussi Jaaskelainen.
The away team should have levelled the scores on the 23rd minute when a mistake by Emerson Thome left Bellamy on a one-to-one with Jaaskelainen, but his attempt was well wide.
Bolton's defence looked very shaky at times and when Ivan Campo gave away a corner Jaaskelainen had to be on top form to save a fierce Bellamy shot.
Towards the end of the half Shay Given in the Newcastle goal did well to get in the way of a well struck Jay-Jay Okocha shot.
The second half saw little in the way of clear cut chances, but good work by Wanderers on both flanks kept the Magpies pinned in their own half for long periods.
Newcastle's away form continues to be a problem and that was typified as they could not force their way back into the game in the second half.