Weber-Shirk graduated in 1985 from Goshen College with a B.A. in physics. He completed his Ph.D. in 1992 in environmental engineering at Cornell University. Weber-Shirk began teaching at Cornell in 1995.
As the founder and director of AguaClara at Cornell University his research interest is to develop robust, sustainable municipal scale drinking water treatment technologies. Since 2004 he has led the AguaClara team to develop low cost infrastructure that produces safe drinking water using local materials and without using any electricity.