Phil Dowson's men delivered a 55-5 home success as they bounced back from the 48-22 defeat in the Premiership Rugby Cup opener at Ealing Trailfinders six days earlier.
The bonus point was in the bag for Saints before the break, and they continued to frustrate a Cambridge side who applied some pressure in the 22 but were regularly unable to make it count.
Youngsters Henry Pollock and Toby Thame both bagged two tries for the black, green and gold, with debutant Tom Seabrook, Archie McParland, Will Glister and George Hendy also on the scoresheet.
Saints, who once again named a blend of youth and experience, were on the front foot from the start, piling the pressure on Cambridge and earning an early penalty, which skipper James Grayson slotted with ease.
It wasn't long before the first try arrived as Tommy Freeman, starting at outside centre, showed his class, leading a breakaway before releasing Seabrook, who turned on the turbos on the left wing before scoring behind the posts.
Grayson converted, and the gap between the sides was starting to become very clear as Saints soon scored again. Pollock was the man to find space on the left as he dived over in the corner.
Grayson added the extras impressively from the touchline to make it 17-0 after just 10 minutes.
Saints were then forced into defence mode as Cambridge finally set foot in the home 22, earning a couple of penalties and kicking to the corner in a bid to crank up the heat.
But Saints repelled the attacks while trying to rediscover the early spark they had shown.
Cambridge had certainly grown into the game as the clock ticked towards the 25-minute mark, but they had nothing to show for their efforts.
And Saints should have had a third try when Glister charged forward, however the final piece of combination play resulted in a knock-on from McParland, who couldn't quite pouch a pass that was just behind him.
But Saints did score soon after as tidy interplay between Grayson and Seabrook allowed centre Thame to force his way over the line.
Grayson saw his conversion attempt skim off the left post and go wide, but he was soon on target after Hendy's fine offload set up Thame for a second try in quick succession.
It meant the try bonus point was wrapped up for Saints before the clock even struck 35 minutes - and there was still time for another score ahead of half-time.
Glister led the breakaway and Grayson took on the charge, flying forward before being floored, but he found the final pass, offloading to the onrushing McParland, who dotted down.
Grayson got his breath back before converting in comfortable fashion to take the score to 36-0 at the break.
Cambridge came out determined to get on the scoreboard at the start of the second period, and they kicked another series of penalties to the corner.
But again the away side failed to make any real inroads, and once again they were made to pay at the other end of the pitch.
Saints moved the ball swiftly from left to right, where Glister was lurking to score his third try in two cup games.
Grayson saw his conversion rebound off the post before Curtis Langdon almost produced a superb 50:22, only to see his kick go out of play just inches in front of the Cambridge 22.
Hendy then delivered a piece of opportunism of his own as he spotted an intercept chance and grabbed the ball well before sprinting in for the score.
Grayson converted and Saints were now just two points shy of a half-century.
They only had to wait a little while longer to reach it as Pollock stripped Cambridge of the ball and gave it to Tom Cruse. The hooker showed a good turn of pace and excellent awareness before sending the ball back inside for Pollock, who dived over the line in eye-catching fashion.
Grayson converted, but Cambridge finally responded with 66 minutes played as winger Eli Caven just managed to find enough speed needed to get to the line.
Saints opted to play the final six minutes with 14 men as Seabrook walked off gingerly following a strong debut, applying some ice when he got to the bench.
But it wasn’t to matter as there were no further scores, the game petering out as Saints savoured their first success of the season.
Saints: Hendy; Glister, Freeman (Litchfield 40), Thame (J Matavesi 62), Seabrook; Grayson (c), McParland (Garside 51); E Waller (A Waller 51), Langdon (Cruse 51), Millar Mills; Atuanya (Cherry 71), Lockett (Logan 65); Vukasinovic, Pollock, Moore-Aiono.
Cambridge Rugby: Tarrant, Green, Hema (Williams 59), Hanks (Hoppe 59), Caven; Steff James, Dabell (Duffy 51); Elwood (Morley 49), Brownlie (Veness 49), Collins (Walker 49); Bretag Norris (c), Baxter; Sloot (Frost 40), Adams, Cardew (Dawson 51).
Referee: Jonathan Cook