Johnson has been considered one of the three leading African-American preachers of the early 20th-century, along with Vernon Johns and Howard Thurman.

Offered a faculty position at the college upon graduation, he taught English and economics and served a year as acting dean.

Following a brief stint as secretary of the western region of the Student YMCA, in 1917 he became pastor of the First Baptist Church in Charleston, West Virginia.

On June 26, 1926, at the age of 36, Johnson was unanimously elected the eleventh President of Howard University, becoming the first African American to serve as the permanent head of that institution.

National honor societies, including Phi Beta Kappa, were established on the campus of Howard.

He traveled 25,000 miles a year throughout the country speaking principally on topics such as racism, segregation, and discrimination.

In 1929, the National Association for the Advancement of Colored People (NAACP) awarded Johnson the Spingarn Medal (its highest honor at that time), for Johnson's ability to secure annual federal funds to support the university's financial future.