Since racing the RC143 at the Isle of Man TT race in 1959, Honda was determined to win in the 125cc class. After the RC143 won Honda’s first victory in 1961, the newly developed RC145 won all 10 grands prix the following year. Although in 1963 the RC146, and in 1964 the 2RC146 won 9 races giving Honda the championship, in 1965 the two-stroke manufacturers dominated, Honda finishing the season with only one victory despite doubling its efforts to win the championship with the 4RC146 from Round 5, and the RC148 in the final round.
As a successor to the RC148, Honda introduced in 1966 the world’s first 5-cylinder 125cc road racer, the RC149. The new machine was powered by a newly developed air-cooled 4-stroke DOHC 5-cylinder engine, achieving a maximum output of 34PS at an ultra-high 20,500rpm. Luigi Taveri, world champion for Honda in 1962 and 1964, rode the RC149 to victory in 5 of the 9 grands prix in this season, winning back the 125cc class title, contributing to Honda’s historic feat of dominating the constructor's' championship in 5 classes (50cc, 125cc, 250cc, 350cc and 500cc). As Honda had ceased its activities in the 50cc and 250cc classes in 1967, the RC149 became the last 125cc class machine to race in Honda’s first era of World GP racing.