The wrecking-ball England forwards played their first game together for Saracens, Mako breaking tackles at will after arriving as a try-scoring substitute and Billy rampant throughout.
Billy arrived from Wasps to join his elder brother during the summer but Mako, who enjoyed a successful British and Irish Lions tour to Australia, was the more destructive.
England under-20 hooker Jamie George crossed twice in the first half to help Saracens establish a comprehensive 21-10 half-time lead.
Owen Farrell kept the scoreboard ticking over with 22 points to ensure the outcome was never in doubt.
Fears that Irish face a long season spent battling relegation were given weight by a result that suggests they will struggle following their summer exodus of players.
Their highlight was supplied by England wing Marlon Yarde, who cut short treatment for cramp to join the end of a backs move that finished with him touching down.
Saracens’ superiority was evident from the start as Irish were pinned back on their goalline with George easily shrugging off a feeble tackle by Sailosi Tagicakibau.
Farrell kicked the conversion to add to an earlier penalty, but the Exiles responded with a fine passage of play sparked by fly-half Ian Humphreys’ smart offload to full-back Topsy Ojo.
Humphreys landed three points, No.8 Jon Fisher burst from the base of a scrum and Ojo showed his strength with a determined run as Saracens came under pressure.
Irish soon trailed 13-3 after Farrell slotted a second penalty.
Saracens’ second try followed shortly after when George darted over as the Exiles’ defence was exposed once more.
Irish responded brilliantly with blindside flanker Kieran Low taking David Paice’s pass and running half the pitch to crash over, evading tackles en route to the line.
Humphreys converted, but Farrell was doing a fine job of keeping the scoreboard ticking over as he slotted penalties either side of half-time.
The rampaging Mako Vunipola was a thorn in Irish’ sides and in one move he secured the turnover before popping up on the final pass to power over as Saracens celebrated a third try.
Lions prop Matt Stevens was sin-binned for a shoulder charge and Irish capitalised on the extra player through Yarde as a pre-planned scrum move paid off.
Saracens were guilty of a lack of ambition in the closing stages, but finally secured the fifth point courtesy of a superb finish by Chris Ashton in the final act of the game.