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Mesler was born in Buffalo, New York, and is Jewish. He attended City Honors School in Buffalo, graduating in 1996.
Mesler attended the University of Florida in Gainesville, Florida, where he competed as a decathlete for the Florida Gators track and field team from 1997 to 2000. He graduated from the University of Florida with a bachelor's degree, with honors, in exercise and sports science in 2000.
Mesler won a gold medal as a pusher for driver Steve Holcomb's U.S. Olympic team in the four-man event at the 2010 Winter Olympics.
Mesler's team finished seventh in the four-man event at Turin in 2006. He won two medals in the four-man event at the FIBT World Championships with a gold in 2009 and a bronze in 2004.
In March 2011, he was inducted into the National Jewish Sports Hall of Fame.