Padgham started out as a tape operator at Advision Studios, working in recording sessions for Yes and Emerson, Lake and Palmer. From there he went to Landsowne Studios and moved from tape-operator/assistant engineer to head engineer. In 1978, Padgham got a job at The Townhouse, where he engineered and/or produced acts including XTC, Peter Gabriel, and Phil Collins.

Padgham's previous work with Gabriel and Collins led to a long and enormously successful collaboration with Genesis in the 1980s, which produced a string of hit albums and singles including Genesis and Invisible Touch. In addition to his work with Genesis and XTC, Padgham co-produced two albums with The Police: Ghost in the Machine and Synchronicity.

In the 2000s Padgham had immense success with Sting as well as McFly. He enjoyed four (4) number hits in 2005 and 2006 with McFly as well as Eight Top Ten Singles. In 2002, Padgham produced The Tragically Hip album In Violet Light, which includes the fan-favorite "Its a Good Life if You Don't Weaken". Padgham has recently produced and engineered the debut album from I Was a Cub Scout, I Want You To Know There Is Always Hope.

Recent work includes developing his own recording studio, Sofa Sound, available commercially in 2007.