The daughter of the children's TV presenter Johnny Ball and his wife Julia (née Anderson, divorced when Zoë was two), Ball was educated at Heston Junior School in west London between 1975 and 1978. Her family then moved to Farnham Common in Buckinghamshire. She attended Farnham Common First School and Farnham Common Middle School before moving to Holy Cross Convent School in Chalfont St Peter and Amersham College of Art and Technology.

Ball was born in Blackpool, Lancashire, and grew up in Farnham Common, Buckinghamshire. She attended Holy Cross Convent School in Chalfont St. Peter, and also attended the Young Theatre at Beaconsfield where she trained as an Actress. Her first TV appearance was as a child in the studio audience of the 1980s Saturday morning children's show, Saturday Superstore, on which her father, Johnny Ball, was appearing as a guest.

She began her television career as a Runner at Granada Television and researcher on BSkyB. She worked as a researcher for quiz shows for two years. Her presenting jobs have included hosting The Big Breakfast and The Priory on Channel 4, BBC One's Saturday morning children's programme Live & Kicking, and the pre-school programme Playdays. In 1994, Zoë Ball presented SMart with Mark Speight and Jay Burridge until she left in 1996. Between 1996 and 1998, she was a regular presenter on Top of the Pops, usually alternating with fellow presenters and DJs Jayne Middlemiss and Jo Whiley.

Although known primarily for her TV work, Ball first worked in radio, after she became co-host of The Radio 1 Breakfast Show on BBC Radio 1 in October 1997 with Kevin Greening. She became the sole host, the first female DJ to do so. At this time, her hard-drinking, hard-partying lifestyle contributed to the identification of the so-called "ladette culture" of the late 1990s. She was twice warned by the BBC for swearing on the radio.

While at BBC Radio 1, Ball began a relationship with the DJ and musician Norman Cook (also known as Fatboy Slim). The couple married at Babington House in Somerset, in August 1999. In 2003, the couple split up when Ball revealed that she had had an affair with a close friend of Cook, fellow DJ Dan Peppe. Ball and Cook were later reconciled.

The couple have a son Woody (born 2000), and a daughter Nelly (born 2010). They lived in a beachfront property in Western Esplanade, Hove.

Ball returned to radio in mid-2002 when she joined London rock station XFM, where she presented the weekday drivetime show until December 2003, and then in January 2004 took over a Friday evening music show for the station. She also stood in for Ricky Gervais while he filmed the second series of The Office. She left XFM at the end of 2004.

In October 2005, Ball became a contestant on the third series of the BBC One talent show Strictly Come Dancing, where she was partnered by Ian Waite. Ball and Waite were ranked in third place; they also scored 38/40 (including two tens) for three dances in the series and one in the Christmas special.

Since 2006, she has provided relief presenting duties for BBC Radio 2, fronted specialist documentaries, sat in for Dermot O'Leary for three weeks in February 2006 and co-presented, with Danny Baker, the hastily conceived replacement for Jonathan Ross' Saturday morning show, in the wake of Ross's suspension due to Sachsgate in 2008.

In September 2007, she hosted a show with Sara Cox celebrating 40 years of BBC Radio 1.

In 2009 Ball became the usual relief presenter for Ken Bruce's weekday mid-morning show on BBC Radio 2. She also began hosting the Saturday breakfast show from 6:00 a.m. to 8:00 a.m. on the network from 6 June 2009 as part of a shake-up of weekend programming at Radio 2. Ball left the Saturday breakfast show on Radio 2; her last show was broadcast on Saturday 28 January 2012. Her replacement in that slot was Anneka Rice. Ball continued on Radio 2 as Ken Bruce's cover.

In 2011, she took over from Claudia Winkleman as the host of Strictly Come Dancing's sister show It Takes Two, airing every weeknight on BBC Two and in 2014, co-hosted the main show whilst Claudia Winkleman was on leave following serious burn injuries to her daughter.

In November 2013, she co-hosted the BBC One Children in Need telethon, alongside Terry Wogan, Fearne Cotton, Nick Grimshaw and Tess Daly. In 2014, Ball presented a BBC Two spin-off from The Voice UK called The Voice: Louder on Two. The show aired for one series lasting for ten episodes.

In 2014, she supported Marks & Spencer and Oxfam’s Love Mum campaign.

In 2015, Ball hosted EastEnders: Backstage Live, a spin-off show during the EastEnders live week. She co-presented the BBC Young Dancer competition with Darcey Bussell on BBC Two.

On 24 September 2016, the couple announced their separation after 18 years together.

More recently, Ball was reported to have been in a relationship with BBC cameraman Billy Yates for several months. On 4 May 2017, Yates was found dead at his home in south London. It is understood that Yates died by suicide, and was depressed after falling victim to a financial scammer.

In March 2018, Ball took part in the 'Hardest Ride Home' challenge, which saw her cycling from Blackpool to Brighton for Sport Relief and mental health awareness. She set off on 5 March for five days. Highlights of the challenge were broadcast in a one-off documentary, airing on 21 March 2018 on BBC One.