It crosses through the eastern section of the University Belt area in a generally east–west orientation between the Nagtahan Interchange and the intersection with Nepomuceno Street in Quiapo.

The street was named after Filipino legislator and resident commissioner to the United States, Benito Legarda y Tuason.

It heads due west, traversing the southern edge of Sampaloc and skirting the northern boundary of San Miguel.

Notable establishments on Legarda Street include Arellano University, Santa Catalina College, the main campus of ABE International Business College, San Lorenzo Ruiz Student Catholic Center, Mendiola Theater and the Department of Social Welfare and Development–NCR Office.

On May 1, 2001, Legarda Street was the site of riots initiated by pro-Estrada protesters being pushed back from Malacañang Palace by police authorities during EDSA III.