Wu attended several educational institutions, including Sixian Elementary School, Xintai Junior High School, Provincial Taiwan Physical Education School, and Fu Jen Catholic University's Department of Physical Education. He was active in judo and Taekwondo, winning the provincial Taekwondo championship three years consecutively and earning a place at Taichung Physical Education School as a reserve athlete for the Asian Games. He later pursued higher education at Fu Jen Catholic University in 1993. Wu's sports career included 23 championships and 135 medals, including a win at the 1985 Southeast Asia Taekwondo Championship in Thailand. However, due to a shoulder injury and family financial issues, he shifted his focus away from sports. During his military service, he served as a Taekwondo instructor in the Military Police Corps.
In 1988, Wu was discovered by representatives from Flying Disk Records and Kaili Creative Group while working at a street stall. After his initial reluctance, he auditioned and later signed with Zheng Dong Records in 1996. His career was temporarily paused in February 1997 for military service, during which he struggled with ongoing shoulder issues, leading to multiple surgeries and reassignment to a lower physical status by September 1998.
Wu's post-military career includes founding Beijing Straw Bear Film and Television in 2003, which handles artist management and entertainment projects. The company began developing animated films in collaboration with Japan's Tezuka Productions and later took over Taiwan's Flying Disk Entertainment. In 2012, Wu established Beijing Straw Bear Technology Co., Ltd. to focus on online and iOS games. He also founded the Nicky Wu Studio in 2014 and partnered with Hong Kong's Solar Entertainment Culture and Macau's Suncity Group to manage music rights and digital content. In 2018, he re-established Flying Disk Entertainment in Taiwan.
Regarding his personal life, Wu dated Cai Yu Lun shortly after his debut, and from 1991, he was in a two-year relationship with Vivian Hsu. In 1999, he was involved in a three-year relationship with Hong Kong actress Ada Choi. Wu married actress Ma Ya Shu on December 13, 2006, but they divorced on August 11, 2009. On November 13, 2013, Wu publicly announced his relationship with Liu Shi Shi, and they married on January 20, 2015, in Beijing. Their first son was born in Taiwan on April 27, 2019.