Jennifer Aniston, George Clooney, Gwyneth Paltrow, David Beckham, Kylie Minogue and Will Smith also sent recorded video messages for the sombre televised event to lend their support to the campaign, which was launched in the U.S. in 2008 by late Spider-Man franchise producer Laura Ziskin.
A clip by soccer ace Beckham kicked off the telethon, with the star stating, "Tonight you'll help change thousands of lives... it's down to all of us to make a difference", while Aniston added: "This is Stand Up To Cancer and wherever you are in the U.K. this evening, we need your help, because this is the end of cancer."
Girls Aloud star Cole was the first performer, singing hit track Call My Name - although technical difficulties with her microphone meant viewers couldn't hear the first half of the tune - while Lewis also took to the stage later on in the evening.
In a pre-recorded heart-wrenching video, cancer survivor Minogue highlighted the seriousness of the disease: "My grandmother, my father, and me. With one in three of us developing cancer in our lifetime, the odds are that each and every one of us will be touched by cancer in some way - but we're at a turning point and, with your help, we can change the odds. Your money will help guarantee vital research needed to help millions more survive cancer, and bring forward the day when all cancers are cured."
Jackson was in the studio to appeal for viewers' donations, and he declared, "Tonight I am here for one simple reason - to kick cancer's a**! But me standing here on a stage won't bring the treatments we so desperately need - I need you to donate whatever you can to join the fight against cancer."
There was light relief during the night when actors Max Beesley, Stephen Graham, Tom Felton and Warwick Davis took part in an all-star version of hit British quiz show The Million Pound Drop, winning $320,000 (£200,000) for the charity appeal.
Boy band JLS also garnered laughs starring in a clip in which they fooled their singer pal Olly Murs into thinking he had killed group member Aston Merrygold during a cannon stunt gone wrong.
Entourage star Piven appeared on the show later in the evening and opened up about his father's cancer battle, saying, "My father passed away from cancer 10 years ago and so it's been incredibly close to my heart. It's an honour to be here and to be part of this."
At the end of the fundraiser, hosted by presenters Davina McCall and Alan Carr, along with Dr. Christian Jessen, the total raised stood at $10.2 million (£6.4 million).