The match at Providence Park was Newcastle’s third American friendly on their tour as they continue preparations for the new season.
However, two goals in a minute in the second half from Rolando Aarons was not enough to rescue the visitors who were facing the prospect of a heavy defeat before then.
Georginio Wijnaldum, who joined Newcastle on a five-year contract earlier this month, scored in the sixth minute to give his new side an early lead.
The Timbers reserve side, who play in the third tier in America in the United Soccer League, hit back to shock Steve McClaren’s team and race into a 4-1 lead.
Adbul Fatawu Safiu scored the equaliser for Portland after 13 minutes before Anthony Manning’s header gave the home side the lead.
Taylor Peay’s rebound from a Portland corner made it 3-1 on the half hour mark before Nick Besler scored in the 70th minute to stretch his side’s lead.
Aarons then struck twice in quick succession with 15 minutes remaining to give his side hope of levelling the match but the Timbers held on for the victory.
Newcastle defeated the Sacramento Republic 1-0 on Saturday.