His father James was a grocery wholesaler and his mother Tammy Reynolds a salesperson. He is the youngest of four brothers; two of them are currently employed as police officers.

Ryan is probably best known for the movie Van Wilder by National Lampoon, though he also starred for four years in the American TV series Two Guys, a Girl and a Pizza Place playing medical student Michael "Berg" Bergen. Ryan had a cameo in 2004's Harold & Kumar Go to White Castle playing a nurse, and has appeared in The In-Laws, with Michael Douglas and Albert Brooks, and the Canadian production Foolproof (2003). In 2004, he co-starred in the action/horror flick Blade: Trinity, as Hannibal King. In 2005 he starred in the film Waiting... playing super-cool waiter Monty. Reynolds also went into serious territory, as the main character George Lutz, who eventually goes psychotic in the horror movie remake The Amityville Horror.

In December 2004, David Goyer (writer of the Blade trilogy and Batman Begins) announced plans to write and direct a major motion picture starring Reynolds as the Wally West version of the Flash.

Since 2002, he has been romantically linked to Canadian singer Alanis Morissette, to whom he has become engaged. The couple lives in Ottawa, Ontario, Canada, in the penthouse suite of newly-built lofts downtown and in Los Angeles, California, USA.

Reynolds has often been sarcastically described as "the poor man's Jason Lee."