The 51-year old currently heads the Biomechatronic Group at the MIT Media Lab, where he has developed what have been described as "the most sophisticated ankle prostheses in the world".
The Princess of Asturias Awards announced the prize winner on Wednesday.
Recognized as the world leader in the field of bionics and biomechanics, Herr had both legs amputated below the knees when he was 17-years-old after suffering severe frostbite while mountain climbing.
The experience saw him focus his efforts on working to improve the mobility of people with disabilities.
His designed prosthetic legs for himself that allow him to continue his passion for rock climbing.
Watch his inspiring Ted Talk:
In awarding the prize to Dr Herr, the Princess of Asturias jury committee acknowledge that he had “opened up new lines of research, resulting in a class of biohybrid, “smart” prostheses which are accelerating the merging of body and machine and amplifying endurance and strength.
“His methods embrace a whole range of scientific and technological disciplines, from biomechanical science and the control of biological movements to the design of biomedical devices. His achievements have had a significant impact on people with physical disabilities through adaptive knee prostheses for femoral amputees and ankle and foot orthopaedic prostheses for clubfoot and pathologies caused by cerebral palsy or multiple sclerosis.”
In a statement, Herr said he was "deeply moved" by the prize.
"It is my hope that this recognition will shed light on the global mission to end human disability in the 21st century through continued advancements in bionics," he said.
Last week it was announced that British historian and academic Mary Beard won the award in the field of Social Sciences for her "outstanding contribution to the study of the culture, politics and society of classical antiquity".
Each of the Princess of Asturias Awards comprises a Joan Miró sculpture, representing and symbolizing the Awards, a cash prize of €50,000, a diploma and an insignia. The awards will be presented in the autumn in Oviedo at a grand ceremony presided over by King Felipe VI and Queen Letizia of Spain.