The fixture began in explosive fashion as both teams scored twice inside the opening 32 minutes.
Brentford's second goal was certainly from a Newcastle perspective, as Harvey Barnes carelessly passed the ball straight to Yoanne Wissa, who gleefully drove at the Magpies backline before firing past Nick Pope.
Barnes atoned for his error by scoring the equaliser, but Newcastle could not match Brentford in the second half as goals from Nathan Collins and Kevin Schade wrapped up the three points.
Collins' goal came from a free-kick lumped forward by Brentford goalkeeper Mark Flekken while Sandro Tonali's soft turnover led to Schade's strike, underlining how easily the Magpies gave up goals.
The loss was Newcastle's fifth of the season and extended their winless run to a fourth game as they sit 12th on the ladder.
Read more football news
Michail Antonio in stable condition after car crash as West Ham send thoughts and prayers
Huge VAR change called for by ex-Premier League star after 'bad' Rico Lewis red card
It also continued the Magpies' poor away form this term, having won on the road just twice.
Speaking to Newcastle's in-house media team after the contest, Guimaraes opened on his frustrations at the defeat as Eddie Howe's side slipped further away from the European spots.
"First half, we have some good moments," Guimaraes said.
"But the second [half], we became a mess. After the third goal, we lost our way, we lost control. We became a mess on the pitch. Very disappointed."
Most read in Football
Jude Bellingham pulls out new celebration as Real Madrid star breaks LaLiga record
Eddie Howe 'under pressure', Andre Onana shocker with Brentford star tipped for elite move
Chelsea forced me to sign for Tottenham but I dislike Spurs as much now as I did then
Huge VAR change called for by ex-Premier League star after 'bad' Rico Lewis red card
Worryingly for Newcastle, the four goals shipped against Brentford made it seven goals conceded in two games after the club's pulsating 3-3 draw against Liverpool on Wednesday.
Played in front of a raucous St. James' Park, Newcastle appeared to have turned a corner with an impressive performance against the league leaders.
But the Bees brought out the worst in Howe's side, sparking serious questions about a defence that just two seasons ago conceded only 33 league goals across the entire campaign, eight more than they have this term after 15 games.
However, Guimaraes does not believe it's a problem isolated just to the backline.
"We have been conceding a lot this season," Guimaraes said.
"We've got Champions League and we didn't concede as much as we have.
"This is not a problem about just the defence. It's a problem for the midfield, a problem for the attack. It's the team's problem.
"We have to stop this. But our season, being honest, has been very, very disappointing."
Howe also pulled no punches in his assessment of his team's performance and bemoaned the string of individual errors that ultimately proved costly.
"That's the frustration, because before that we looked tight at the back, the issues were at the other end of the pitch," Howe said.
"Now we've scored five in two games and looked a really good attacking team, some of our attacking work was really strong today.
"Lo and behold we then we go and concede seven in two games from nowhere really. It's difficult to work out because structurally we've been fine but there were a lot of individual errors today.
"We've got work to do in a lot of different areas. There's a very good team in there, I've got no doubts, but we haven't shown it consistently enough, we haven't delivered it anywhere near enough for my liking.
Read More on talkSPORT
I couldn't stand arrogant Ibrahimovic and our fight forced him to leave club within days
Frank Warren thrilled as 'greatest boxing card ever' is confirmed featuring Daniel Dubois
"A period of reflection and a period of work, then we'll try to fight back."
Pep Guardiola reacts to 'harsh' Rico Lewis red card in Man City's 2-2 draw with Crystal Palace
Howe and his Newcastle side will hope to have found a solution to their defensive woes in time for their next fixture on December 14 as they host Leicester City.