Ross studied history at the School of Slavonic and East European Studies (now merged with University College London). Before transferring he also went to the Southampton Institute (now Southampton Solent University), where he is on the alumni list.

Ross married author and journalist Jane Goldman in 1988, when Goldman was 17 years old. They have since had three children: Betty Kitty, Harvey Kirby (named after Jack Kirby and Harvey Kurtzman, two comic book creators whom Ross especially admires) and Honey Kinney. His older brother is Paul Ross, also a television presenter, while two other brothers, Miles and Simon, are both TV producers. His younger brother Adam and younger sister Lisa both work in the media, while his mother, Martha, has been an extra in BBC soap opera EastEnders (as a market stallholder) since the show's inception in 1985.

Ross founded the production company Channel X with Alan Marke in 1987, which went on to produce such successes as The Last Resort, The Incredibly Strange Film Show and One Hour With Jonathan Ross . However, in 1995 he left, despite its profitable nature. He was quoted in a 1998 article as stating:

It was to do with a deliberate change in my life, moving away from TV as the core of my existence to focus on my family more. So I had to give up everything to do with Channel X, and I literally got only A1 for my share, which was unbelievable. Ross is also known for owning exotic pets, and is a big fan of David Bowie, British punk rock, Star Trek, Doctor Who and comic books. Ross has even co-owned a comic shop in London with Paul Gambaccini. He was also the visual inspiration for the main character in the comic book Saviour. In 2006, Ross will make a cameo appearance as a Cyberman in Doctor Who. *

He is a fan of the band They Might Be Giants, and appeared on stage with them during their most recent UK tour.

He was described as "one of the funniest men in the country" by comedian David Baddiel (although Ross has never strictly been a comic).

In 2005, Ross was made an Officer of the Order of the British Empire in the Queen's Birthday Honours for services to broadcasting. He celebrated the news by playing "God Save the Queen" by The Sex Pistols (which was banned by the BBC when released in 1977) on his Radio 2 Saturday morning show. He was also voted Britain's second smuggest person after Robbie Williams, in a poll conducted by Time Out magazine.

Ross's latest announcement is that he is quitting his regular panellist seat on the BBC TV sport/comedy quiz show They Think It's All Over, stating:

I’ve had a great time on They Think It's All Over, imparting my vast sporting knowledge to the nation, but I need time now to focus on my other commitments and so regrettably I won't be back for the 20th series. It's a fantastic show and from now on I'll be able to actually watch it. Ross is also well known for his distinctive long hairstyle, which creates mixed emotions in many viewers. Recently, however, he has cut it somewhat shorter.

In April 2006, reports in the media suggested that Ross was poised to become the highest paid television personality, although the identity as to which broadcaster would be footing this bill was unclear. A tussle between ITV, the BBC and Channel 4 has been predicted in the fight to secure his services. It is reported that he currently earns £530,000 per year for hosting his Radio 2 show.

According to the British tabloid The Sun, Ross is considering a move to Channel 4.

On Friday Night with Jonathan Ross, he claimed he was offered a part in the new Doctor Who series. He said he was offered to be a Cyber-Man in January; however, by January, all the filming was complete. His claim of being offered the part was not corroborated by any other sources.