Montgomery often worked with his brothers Buddy (Charles F.) and Monk (William H.) and with organist Melvin Rhyne. His recordings up to 1965 were oriented towards hard bop, soul jazz, and post bop, but around 1965 he began recording more pop-oriented instrumental albums that found mainstream success. His later guitar style influenced jazz fusion and smooth jazz.

Montgomery was born in Indianapolis, Indiana. According to NPR, the nickname "Wes" was a child's abbreviation of his middle name, Leslie. The family was large, and the parents split up early in the lives of the children. Montgomery and his brothers moved to Columbus, Ohio, with their father and attended Champion High School. His older brother Monk dropped out of school to sell coal and ice, gradually saving enough money to buy Wes a four-string tenor guitar from a pawn shop in 1935. Although Montgomery spent many hours playing that guitar, he dismissed its usefulness, saying he had to start over when he got his first six-string several years later.

He and his brothers returned to Indianapolis. By 1943, Montgomery found work as a welder and got married. At a dance with his wife, he heard a Charlie Christian record for the first time. This motivated him to buy a six-string guitar the next day. For nearly a year, night and day, he tried to imitate Christian and teach himself the guitar. Although he hadn't intended to become a musician, he felt obligated to learn after buying the guitar. He received no formal instruction and couldn't read music. By the age of twenty, he was performing in clubs in Indianapolis at night, copying Christian's solos, while working during the day at a milk company. In 1948, when Lionel Hampton was on tour in Indianapolis, he was looking for a guitarist, and after hearing Montgomery play like Christian he hired him.

He worked as a welder during the day to support his wife and seven children, then performed at two clubs at night until well into the morning. He was a smoker who had blackouts while trying to maintain this busy schedule. During one performance, the audience included Cannonball Adderley, George Shearing, and Lennie Tristano. Adderley was so impressed by Montgomery's guitar playing that he persuaded Orrin Keepnews to sign him to Riverside. Keepnews was also persuaded by a gushing review written by Gunther Schuller. In New York City Montgomery recorded A Dynamic New Sound, the Wes Montgomery Trio, his first album as a leader after twenty years as a musician. In 1960, he recorded The Incredible Jazz Guitar of Wes Montgomery with Tommy Flanagan, Percy Heath, and Albert Heath.