[2] Weatherly began his acting career with a minor television role on The Cosby Show as Theo Huxtable's roommate.

He then met director Whit Stillman, who cast him in the 1998 film The Last Days of Disco as Hap, opposite Chloë Sevigny.

His movie credits include Meet Wally Sparks (1997) with Rodney Dangerfield, Gun Shy (2000) with Liam Neeson, Cabin by the Lake (2000) with Judd Nelson, and the independent film Trigger Happy opposite Rosario Dawson.

He portrayed Jesus Christ in a YouTube video that also featured comedian Sarah Silverman and was sponsored by a pro-choice organization.

[10] CBS announced in January 2016 that Weatherly would be leaving NCIS after 13 seasons of starring as main character Anthony DiNozzo.

[11] At the same time, the network announced he would star in a new series called Bull in fall 2016, loosely based on the real-life trial consultancy of Dr. Phil McGraw.

He directed the 2017 documentary Jamaica Man, about the life of British expatriate Nigel Pemberton, which premiered at the 2017 Telluride Film Festival.

[29] Weatherly and his wife are involved with nonprofit organizations such as the Tryall Fund, which focuses on improving education and public health in Hanover Parish, Jamaica.

[2] During filming of Dark Angel in January 2000, Weatherly began a relationship with co-star Jessica Alba, leading to their engagement in 2001.

[8] In January 2018, CBS settled for $9.5 million with actress Eliza Dushku after she was fired from a recurring role on Bull after informing producers of Weatherly's inappropriate behavior on the set.

[36] According to documents from the official mediation, Weatherly was recorded on video making comments about spanking Dushku over his knee, soliciting a threesome, alluding to sexual assault in his "rape van", and other inappropriate remarks.

"[36] Dushku responded that Weatherly broke the terms of their settlement by speaking to the press and characterized his apology as "more deflection, denial, and spin.