McHale was born in Plano, Texas, the youngest of four children. McHale is descended from immigrants from County Mayo, Ireland. He grew up with Disney Channel actress and singer Demi Lovato. He attended Academy of the Canyons High School in the Santa Clarita Valley in California.
Before becoming an actor, McHale joined the American boy band NLT, which stands for "Not Like Them". They were discovered by Chris Stokes in 2006, who subsequently signed them to his label, The Ultimate Group. On March 13, 2007, they released their first single, "That Girl". The following month, they opened (with Chantelle Paige) for The Pussycat Dolls. The band also made a guest appearance in the film Bratz: The Movie as an auditioning band. While in the group, McHale, along with Timbaland and his bandmates, co-wrote the song "She Said, I Said (Time We Let Go)". On April 30, 2009, member Travis Michael Garland announced that NLT had split.
McHale, who has a record deal with Universal Music Group, writes original music in his spare time. In an interview with Mario Lopez, McHale stated that he plans to pursue solo music post-Glee. In 2015, McHale, Chris Moy, and Justin Thorne co-wrote the song "Heartless" which was featured on the latter's debut EP The Heartbreaker. That same year, he starred in the music video for Thorne's song "Summer Nights".
In 2007, McHale made a guest appearance on NBC's comedy series The Office in the season four episode "Launch Party", portraying a pizza delivery boy who is taken hostage by Michael Scott (Steve Carell). He then guest starred in three episodes of Nickelodeon's teen drama series Zoey 101 as Dooley Fibadoo. In 2008, McHale guest starred in two episodes of HBO's dark fantasy drama series True Blood, appearing as Neil Jones, a coroner's assistant.
In 2009, McHale landed his breakout role as Artie Abrams in the Fox musical comedy-drama series Glee. His character, wheelchair-bound after a car accident, joins the McKinley High glee club in the first episode. He had his first solo performance on the show when he sang "Dancing with Myself" in the episode "Wheels". In the episode "Dream On", he danced in a fantasy sequence to "The Safety Dance", and sang "Dream a Little Dream of Me". In the second season episode "Britney/Brittany", he sang a solo (in a dream sequence) of "Stronger", after being anaesthetized for dental surgery. He also danced in a dream sequence alongside Harry Shum, Jr. to Michael Jackson's song "Scream" in the third season episode "Michael". McHale, along with the main cast of the series, was nominated for the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series four times, winning in 2010.
In 2010, McHale appeared briefly in One Call's music video "Blacklight" alongside former NLT bandmate Justin Thorne, who was a member of One Call. In June 2011, McHale appeared in Katy Perry's music video for her song "Last Friday Night (T.G.I.F.)" as the character Everett McDonald. On July 22, 2012, McHale co-hosted the 2012 Teen Choice Awards with Demi Lovato. In January 2014, it was reported that McHale would host a comedy panel show, Virtually Famous, for the British digital television channel E4. The show also features comedian Seann Walsh and radio presenter Chris Stark as series regulars and team captains.
On February 24, 2014, it was announced that McHale had signed on to play a supporting role in the Kathy Bates and Dustin Hoffman led independent film Boychoir. McHale's character, Wooly, is a young music teacher who helps a troubled young boy at his school. In July 2014, it was announced that he and Aaron Tveit had signed on to star in the comedy film They Might Be Kennedys. McHale will play one of the leads, Teddy Mulligan. In April 2016, McHale joined the cast of Dustin Lance Black's drama miniseries When We Rise as AIDS activist Bobbi Campbell.
In September 2012, McHale and his dog Sophie appeared in a PETA ad campaign, promoting the adoption of shelter animals. In June 2016, the Human Rights Campaign released a video in tribute to the victims of the 2016 Orlando gay nightclub shooting, in which McHale and other celebrities told the stories of the people killed there. In September 2016, he co-created the mobile app +ONE, created with the intent to "provide people with one app to simplify the process of creating events." He resides in the Hollywood Hills in a $1.025 million mid-century home.