A child student at Corona Stage Academy, he appeared in a succession of commercials and children's films in the early 1970s, and first gained national recognition at the age of seventeen through the sitcom Butterflies, in which he played the character Adam. He then played the teenage son of Norman Stanley 'Fletch' Fletcher in Going Straight before achieving stardom in the series Only Fools and Horses in which he played Rodney Trotter, the younger brother of the main character Del Boy.

This programme started as a small comedy in 1981 and rapidly grew in popularity until it reached its peak in 1996 with its Christmas Day episode gaining the largest audience ever obtained by a fictional TV show in the UK. During this period, Lyndhurst also starred in ITV sitcoms The Two of Us and The Piglet Files, as well as a number of stage shows.

In 1993 he played the lead character of Gary Sparrow in science fiction sitcom Goodnight Sweetheart. At around the same time, he was also the face and voice on the TV and radio commercials for the telecommunications chain People's Phone.

In between 1997 and 1999 Nicholas Lyndhurst was the public face of the stationery chain store WH Smith, starring as all four members of a family in their adverts. He won a BAFTA for his acting in the adverts.

He is married and has a passion for outdoor activities, including flying aeroplanes, surfing and deep-sea diving.