But Ronan O'Gara - who lost his international place to rising star Jonathan Sexton during the RBS 6 Nations - fired over three second-half penalties and converted Doug Howlett's second try of the game and one from Jean De Villiers to secure a superb Irish comeback.
The tie was the third time the two sides had met this season, with each triumphing on home soil, and it was Munster who shrugged off O'Connell's pre-match fitness test failure to go 3-0 up at Thomond Park thanks to O'Gara.
Ireland international Keith Earls exploited the momentum to jink wide and feed Paul Warwick for the opening try, before Howlett went over following two Myler penalties.
But the visitors were far from overawed and England full-back Ben Foden worked his magic to release Clarke for the Saints' first score after Myler had clipped over his third penalty.
With just three points in it at the break Northampton were never able to relax and were soon trailing again after Tomas O'Leary put in De Villiers for the score.
O'Gara converted before cancelling out a Myler penalty with one of his own and then converting late on after Howlett crossed to snuff out any lingering Northampton hopes.