Her credits include Drowning by Numbers (1988), King Ralph (1991), 101 Dalmatians (1996), Event Horizon (1997), The Patriot (2000), Anonymous (2011), the Hollywood film adaptation of The Girl with the Dragon Tattoo (2011), Endless Love (2014), Red Sparrow (2018), The Turning (2020), The Sandman (2022), and Little Bone Lodge (2023).

Richardson and her sister Natasha's early education began at the independent St Paul's Girls' School in Hammersmith.

She portrayed a teacher on the verge of a nervous breakdown in the 1989 Channel 4 serial Behaving Badly and fictional Finnish Princess Anna (with "a voice like a tuba") in the 1991 screen comedy King Ralph.

In 1996, she played fashion designer Anita Campbell-Green in the Disney live-action remake of the animated 101 Dalmatians opposite Glenn Close as Cruella de Vil.

She was cast in the 2001 film The Affair of the Necklace after director Charles Shyer noticed her resemblance to doomed 18th century French Queen Marie Antoinette.

In 2003, Richardson took on the role of Julia McNamara in the television drama Nip/Tuck, based on the complicated lives of two plastic surgeons filled with romance in Miami.

In 2009–10, Richardson appeared as Catherine Parr, sixth wife of Henry VIII, in the fourth (and final) season of Showtime's hit period drama The Tudors.