The visitors cruised into a two-goal lead through Leon Legge and Toumani Diagouraga and, although Franck Moussa responded, Clayton Donaldson headed a third before Mark Allott struck in stoppage time.
Uwe Rosler's side started well and got the goal they deserved in the 12th minute when a free kick from Sam Saunders was glanced into the bottom corner by Legge.
Brentford scored again in the 59th minute when Saunders broke away and set up Diagouraga, who swept a right-foot shot into the roof of the net from 12 yards.
Chesterfield replied 10 minutes later when Scott Boden fired against a post and Moussa lashed in the rebound in from the edge of the area and only a great save by Simon Moore denied Bowery an equaliser.
Donaldson eased Brentford's nerves when he was left unchallenged to head his 11th of the season from an 80th minute corner and although Allott drove in his first goal for two-and-a-half years from 20 yards, it was too little too late.