Lambert, who took his goals tally for the season to 10, had a hand in - then converted - a spot kick in either half before Guly and Holmes put the gloss on the victory.
The Saints kept their 100% record after five games at St Mary's intact and they have now made their best start to a league season in 52 years although they started sluggishly this afternoon.
Adrian Mariappa, Jonathan Hogg and Joe Garner all had chances to put the visitors in front before John Eustace, under pressure from Lambert, handled in the area.
The much-travelled striker duly slotted home and he made no mistake when he was presented with another opportunity after half-time when he was hauled down by Mariappa.
Guly ensured there was no way back for Watford with a fine finish, while substitute Holmes wrapped up the win with a magnificent strike from long range late on.
However, it was the mid-table visitors who made the better start, surprisingly, with Mariappa heading wide early on.
Hogg shot straight at Kelvin Davis from the edge of the area, while the Saints goalkeeper superbly tipped over from Garner's lob.
To their credit, Nigel Adkins' men weathered the early onslaught and took the lead against the run of play thanks to free-scoring Lambert's 22nd-minute penalty.
The striker slotted past Rene Gilmartin for his ninth goal of the season after Eustace had handballed in the area as he and Lambert battled to reach De Ridder's cross.
Lambert could have doubled his and Southampton's tally immediately after but his header from Daniel Fox's right-wing free-kick struck the post.
The hosts were clearly in the ascendancy and Adam Lallana's volley from just outside the box thundered against the crossbar.
The midfielder then forced Gilmartin to make a fine save from his header as the Saints ended the half strongly.
A scrappy period ensued after the interval although Lambert won another penalty when he was brought to the ground by Mariappa after trying to latch on to Frazer Richardson's cross.
The 29-year-old once again fired left to put his side two goals to the good after 55 minutes and he nearly had a hat-trick but his 25-yard strike fizzed wide.
The Hornets refused to lie down, though, and Davis had to be at his best to deny Craig Forsyth after the midfielder had cut in from the right.
But their resistance was quelled when Guly picked up Lallana's pass before placing the ball into the right corner in the 70th minute.
Richard Chaplow struck the post from the edge of the area, while Richardson forced another fine save from Gilmartin as Southampton laid siege to the Hornets' goal.
And they were rewarded two minutes from end as Holmes' fantastic curling effort from 25 yards ensured an emphatic win.