Santos was born in Pasig, Rizal, Philippines (now a part of Metro Manila) - as Lope C. Santos - to Ladislao Santos and Victoria Canseco, both natives of Rizal province. He used Kanseko instead of Canseco for his middle name to show his nationalism. During his times the letter C is not included in the Tagalog alphabet. Santos studied at Escuela Normal Superior de Maestros (Normal Superior School of Teachers) and Escuela de Derecho (Law School); and got his Bachelor of Arts degree in Colegio Filipino (Filipino College). He became an expert in dupluhan, a popular poetical debate competition in his time, which can be compared to balagtasan, a similar contest but with shorter discourse.
In 1900, he served as editor on publications written in Tagalog, such as Muling Pagsilang (Rebirth) and Sampaguita, which he founded. Through Philippine President Manuel L. Quezon, he was appointed as director of the Surian ng Wikang Pambansa (National Language Institute).
Santos became governor of Rizal province from 1910 to 1913, and governor of Nueva Vizcaya from 1918 to 1920. During the 5th Philippine Legislature, he also served as Senator in the Twelfth District under the Nacionalista Party.
In February 10, 1900, Santos married Simeona Salazar and they had 5 children. He had an operation for his liver disease but later died. Santos' last request on his deathbed was to make Tagalog a National Language of the Philippines.
The works of Santos include the following: