Wood made his film debut in 1989 with a small part in Back to the Future Part II. He went on to achieve recognition as a child actor with roles in Avalon (1990), Paradise (1991), Radio Flyer, Forever Young (both 1992), The Adventures of Huck Finn and The Good Son (both 1993). As a teenager, he starred in films such as North, The War (both 1994), Flipper (1996), The Ice Storm (1997), Deep Impact and The Faculty (both 1998). Following the success of Lord of the Rings, Wood has appeared in a wide range of films, including Eternal Sunshine of the Spotless Mind (2004), Sin City, Green Street, Everything Is Illuminated (all 2005), Paris, je t'aime, Bobby (both 2006), Celeste and Jesse Forever, Maniac (both 2012), Grand Piano (2013), The Last Witch Hunter (2015), The Trust (2016), and I Don't Feel at Home in This World Anymore (2017).
Wood's voice work includes the role of Mumble in Happy Feet (2006) and its sequel; the title character in 9 (2009); and Spyro in the Legend of Spyro video game trilogy (2006–2008). In addition, he provided the voice of Beck on Disney XD's Tron: Uprising (2012–2013), and Wirt in the Cartoon Network miniseries Over the Garden Wall (2014). From 2011–2014, Wood played the role of Ryan Newman on the FX television series Wilfred, for which he received a Satellite Award nomination for Best Actor. From 2016–17, he starred as Todd Brotzman on the BBC America series Dirk Gently's Holistic Detective Agency.
Wood has his own record label, Simian Records, which he founded in 2005. In 2010, he founded the production company SpectreVision, which specializes in producing horror films.