Kaplinsky's parents are Raphael Kaplinsky, an exiled Jewish South African economics professor at the Open University, and his wife Catherine Kaplinsky née Charlewood, a psychotherapist.

Her paternal grandparents originated from Slonim (then in Poland, now in Belarus), and emigrated to South Africa in 1929. Kaplinsky was born in Brighton, but spent her early life in Kenya (where she claims to have been fluent in Swahili), although she later returned to England, where she was brought up in Barcombe, East Sussex. She attended Ringmer Community College, until the age of sixteen when she moved to Varndean College in Brighton.

After graduating in English from Hertford College, Oxford in 1995, one of her first jobs was working in the press offices of Labour leaders Neil Kinnock and John Smith.

Kaplinsky was the subject of one of a series of BBC television programmes, Who Do You Think You Are?, in which well-known people trace their family trees. Kaplinsky's programme was broadcast on 6 September 2007. She followed her paternal line to Slonim and was shown official documentation relating to her cousin's family. This included the death of family members during the "liquidation" – massacre – of the Slonim ghetto by the Nazis and another's escape to the partisans and eventual emigration to Australia. Her maternal line included an apothecary to King George III.

Kaplinsky started out presenting on F2F, a youth chat show, for LWT's Talk TV in 1996 with co-host Sacha Baron Cohen. She then moved to presenting early morning news bulletins at Meridian. Within six months she was co-presenting their evening news programme Meridian Tonight. In 1999 she moved to ITV's London News Network where she hosted London Today and London Tonight and a political programme called Seven Days.

In November 2000, she moved to Sky News, where she co-presented Live at Five with Jeremy Thompson, as well as the breakfast news programme Sunrise.

Kaplinsky joined the BBC to present BBC Breakfast in November 2002, from Monday to Thursday alongside Dermot Murnaghan, following the departure of Sophie Raworth to present the BBC News at Six. Kaplinsky eventually left Breakfast in May 2005, to become an occasional presenter on the News at Six. Kaplinsky also acted as main weekday presenter on the News at Six, when Sophie Raworth was on maternity leave in October 2005. She was replaced as the main Weekday presenter on Breakfast by Sian Williams.

In 2006, Kaplinsky became only the third woman to present the BBC's BBC Ten O'Clock News, after Fiona Bruce (regular presenter) and Sian Williams who had co-presented the programme from the studio in Westminster with Huw Edwards in April 2005. She continued to present on the programme occasionally in 2007, and was also been on the BBC One O'Clock News.

From mid-2007, Kaplinsky took part in a trial on BBC One in Birmingham, where she presented a special news update at 8 pm, between 60-90 seconds long.

On 5 October 2007 the BBC confirmed that Kaplinsky had decided to depart the BBC to become a presenter of Five News. She presented her last Six O'Clock News on 5 October with former Breakfast colleague Dermot Murnaghan. Her BBC salary was a reported £175,000 and her salary at Five was reported to be "in excess of" £300,000. This is believed to make her the highest earning newsreader in Britain.