Welch was born in Austin, Texas, United States, although his family soon relocated to Boston, Massachusetts. His musical education was helped by his access to his father's record collection, which included work by Magic Sam, Earl Hooker and B.B. King, and more rock orientated recordings by the Beatles and the Rolling Stones. It was the effect of Albert King's work that caused the youngster to gravitate towards the blues, and he learned to play the guitar at the age of eight. Three years later his parents allowed him access to blues jams and clubs in the Boston area, and he learned further skills from musicians such as Ronnie Earl and Luther "Guitar Junior" Johnson. In 1992, Welch played at the opening of the first House of Blues club in Cambridge, Massachusetts. The club's co-owner, Dan Aykroyd, changed his nickname from "Little Mikey" to "Monster Mike." Within a short while the Monster Mike Welch Band was formed with George Lewis on guitar, Jon Ross on bass and Warren Grant on drums. They got named at the 1995 Boston Music Awards as the "Best Blues Act". With this line-up Welch released three albums on Rounder Records, Tone-Cool subsidiary. His early albums secured his place as an international touring act, and included These Blues Are Mine, and Axe to Grind. He was quoted in People magazine as "being an adolescent is more than enough blues for anyone to handle". In 1997, Welch played at the Notodden Blues Festival. Catch Me followed in 1998, when Welch was still a teenager. Catch Me saw David Hull compose one track and play bass guitar on the album. The early attention came at a price. Welch later explained, "I struggled with that all the time... I think it's a large part of the reason why my early records are all original songs," he said. "It wasn't because I didn't want to record versions of some of my favorite songs, it was because I felt like I needed to give people something that wasn't as simple as guitar acrobatics from a novelty act.... I think some of my decisions were compensation for not wanting to be seen as immature or shallow." In 2003, Welch contributed to the Severn Records release, Sugar Ray & The Bluetones Featuring Monster Mike Welch. It sparked the beginning of a long working relationship with that band. Adding Insight to Injury was Welch's next solo release in 2004, which included a cover version of Bob Dylan's song "Masters of War". However the album was not a commercial success. By way of diversion, Welch moved briefly to France and backed the French harmonicist, Nico Toussaint, on a tour. Welch's next album release, Cryin' Hey! Monster Mike Welch Plays the Blues, was issued solely in Europe on BGB Records. Around this time Welch took the opportunity to twice play alongside Johnny Copeland. Welch went on to perform and record with Duke Robillard, Nick Moss, Johnny Winter, Darrell Nulisch and the Knickerbocker All-Stars, which featured Jimmie Vaughan. Welch has also appeared on recordings by the Mannish Boys and contributed to Fifty Shades of Blue, by Anthony Geraci and the Boston Blues All Stars. He was also a guest performer on Billy Price's 2015 album, Strong. In addition, Welch continued to work with Sugar Ray Norcia, more recently issuing Seeing is Believing on Severn Records in October 2016. Earlier that year the act had played at the Hawaii Theatre in Honolulu. In June 2016, Welch and singer Mike Ledbetter took part in a tribute to Otis Rush at the 33rd Chicago Blues Festival. Ledbetter had previously fronted the Nick Moss Band, and the Welch and Ledbetter live collaboration led to them recording an album together. Welch stated "... from the first time I heard Mike, I knew he was the kind of singer I’ve always been trying to play like." Ledbetter countered, "The way we played off each other was beautiful to me... Everything just fit perfectly." The album was titled Right TimeRight Place and was released by Delta Groove Productions. Right Place Right Time's track listing included a number of original songs and several cover versions. These latterly comprise the album's opening track, a cover of Elmore James' "Cry for Me Baby"; the Willie Dixon penned "I Can't Stop Baby"; alongside a reworking of the Jerry Leiber and Artie Butler song "Down Home Girl"; plus "Cryin' Won't Help You", which was an old B.B. King song. Ledbetter died at his home in January 2019, aged 33, of complications from epilepsy. Welch was nominated for a Blues Music Award in 2017, 2018, and 2019. He won the Award for 'Instrumentalist - Guitar' in 2019.
