Martin Allen's team wrapped up their second win of the season with a second-half brace from Isaiah Rankin and could have had more goals.
Chesterfield had shown their usual fighting spirit to draw level in the first half but Brentford were the better side and on the evidence of this display, will be a force in League One.
The only worry for Allen was an injury to his Icelandic midfielder Olafur Skulason who limped out of the match after 38 minutes.
Chesterfield also had injury problems and face being without their promising right-back Alex Bailey for five weeks with a knee injury.
Roy McFarland's squad is not big enough to cope with injuries and there is a chance he will try to bring in a player on loan.
On the night, Brentford certainly deserved to take the points and they were given an excellent start by defender Sam Sodje, who headed a 14th-minute corner in at the near post.
Chesterfield responded and equalised in the 27th minute when Paul Hall scored on his home debut with a low shot from 10 yards after the visitors failed to cope with a cross from the right.
After the break the pace and power of Rankin proved decisive, as he restored his side's advantage with a 20-yard shot into the top right hand corner in the 52nd minute.
He scored again four minutes later when Chesterfield were unable to combat his strength on the ball and after his first shot was blocked, he placed the rebound into the bottom right hand corner.
Chesterfield might have had a penalty when substitute Tcham N'Toya-Zoa appeared to be held back after Adam Smith delivered a teasing cross form the left, but Brentford substitute DJ Campbell came close to adding a fourth in the closing minutes.