In an eventful first-half at the Estádio da Luz, Gonçalo Ramos' header broke the deadlock before the Magpies responded in quick fashion through Miguel Almirón's close-range finish.
Álejandro Grimaldo's free-kick restored the hosts' lead before Almirón continued his impressive pre-season goalscoring form with a delightful curling finish on the stroke of half-time, the Paraguayan's fourth strike in as many friendly fixtures.
Newcastle were reduced to ten men in the closing stages following Joelinton's red card, for two bookable offences, before Araújo's late winner sealed victory for the Lisbon-based outfit.
The two sides last faced each other nine years ago in the 2012/13 Europa League quarter-finals, with the Portuguese giants prevailing in a 3-1 first-leg victory in Lisbon.
United head coach Eddie Howe handed a start to teenage midfielder Elliot Anderson, a Magpies Academy product since the age of eight who completed an impressive loan spell at newly-promoted League One outfit Bristol Rovers last term.
Almirón, who had netted four goals during pre-season before this evening's clash, was a late introduction to the starting eleven, after Jacob Murphy had originally been selected, but almost got the Magpies off to an excellent start.
The Paraguayan combined neatly with Bruno Guimarães, knocking the ball beyond Morato but steered his cross-cum shot wide of the left-hand post whilst evading Callum Wilson from close-range.
In the 15th minute, Benfica opened the scoring as Ramos latched onto Mario's in-swinging corner, beating goalkeeper Nick Pope to the lofted ball, before heading into an empty net.
Despite the setback, Newcastle found themselves on level terms as Almirón netted his fifth goal of pre-season.
The South American forward began and finished the move, picking out Kieran Trippier on the right wing before the full-back returned the favour with a low cross into the 28-year-old's path, who tucked the ball beyond Benfica goalkeeper Odysseas Vlachodimos.
In the 32nd minute, Benfica regained their one-goal advantage in fine fashion as Grimaldo's 25-yard free-kick sailed over the United wall before finding the far right-hand corner.
Pope produced an excellent double save to prevent the two-time European Cup winners from doubling their advantage shortly after, reacting quickly to push Mario's close-range volley away from goal.
Allan Saint-Maximin went close to equalising for Newcastle as the French winger picked the ball up on the left wing before drilling a low effort into the side-netting, past the stranded Odysseas.
In the 44th minute, United found themselves courtesy of Almirón's smart finish, combining once again with Trippier before curling a low effort into the far left-hand corner.
Howe made eleven changes at the break, with Nottingham-born teenager Matt Bondswell slotting in at left-back while the likes of Joelinton, Joe Willock and Emil Krafth, who signed a new one-year contract extension on Monday, were also deployed from the bench.
Chris Wood went close to sending United in front as the New Zealand international raced onto Joe Willock's pass but his low drive was held by Odysseas.
The Magpies continued their pursuit to take the lead as Jacob Murphy latched onto Jonjo Shelvey's excellent through ball before the 27-year-old winger's strike was turned out for a corner by Odysseas.
Newcastle found themselves down to ten men in the final stages as Joelinton was sent off, with the Brazilian picking up a second yellow card for a foul on Florentino, sparking confrontational scenes on the touchline between the two sides.
With a penalty shoot-out looming, Newcastle conceded a third goal in the 88th minute as Roman Yaremchuk advanced beyond Dan Burn before finding Araújo inside the penalty area, who rifled the ball into the net.
Newcastle United (first half): Nick Pope, Kieran Trippier, Jamaal Lascelles (c), Sven Botman, Matt Targett, Sean Longstaff, Bruno Guimarães, Elliot Anderson, Miguel Almirón, Allan Saint-Maximin, Callum Wilson.
Newcastle United (second half): Karl Darlow, Emil Krafth, Fabian Schär, Dan Burn, Matt Bondswell, Jonjo Shelvey (Matty Longstaff 75), Joelinton, Joe Willock, Matt Ritchie, Jacob Murphy, Chris Wood.
Subs not used: Jay Turner-Cooke.