After Bryan Mbeumo had an early goal ruled out for offside, Newcastle raced into a 2-0 lead with goals from Bruno Guimaraes and Jacob Murphy.
Former United striker Ivan Toney pulled a goal back for Brentford from the penalty spot early in the second half before Guimaraes quickly restored the two-goal advantage.
Miguel Almiron added some gloss to the scoreline with his fourth of the season to make it 4-1.
Joelinton then forced Ethan Pinnock to put the ball into his own net late on to make it 5-1.
1. Nick Pope - 6
Beaten at his near post for Brentford’s offside goal but made a number of decent saves during the afternoon.
2. Kieran Trippier - 8
Up and down the right flank tirelessly all afternoon. Put a great ball in for Guimaraes’ opener.
3. Fabian Schar - 7
Cut things out very well at the back and rarely let Nick Pope get troubled.
4. Sven Botman - 8
Continues to impress at the back for Newcastle. Dealt with Toney’s physicality well and played the ball out from the back well.