Asma al-Assad is among 12 people added to the sanctions list, which already includes her husband.
However, the ban cannot stop her from travelling to the UK, said British officials.
The 36-year-old, who is of Syrian descent but spent much of her life in west London, has generally played a low-key role in the regime.
However, in February she wrote to Britain's Times newspaper to explain why she thought her husband was still the right man to lead Syria.
In the last weeks, the first lady dubbed a "rose in the desert" by Vogue, became the focus of sharp criticism after Britain's Guardian newspaper released e-mails showing the ruling couple shopping for luxury goods as the country slid into bloody chaos.
Other members of Assad's family have also been added to the sanctions list. The AFP news agency says these include Assad's mother, sister and sister-in-law.